NM_007348.4:c.309G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007348.4(ATF6):c.309G>A(p.Ser103Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,610,374 control chromosomes in the GnomAD database, including 12,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1618 hom., cov: 31)

Exomes 𝑓: 0.091 ( 11144 hom. )

Consequence

ATF6
NM_007348.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.513

Publications

17 publications found

Variant links:

Genes affected

ATF6 (HGNC:791): (activating transcription factor 6) This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]

ATF6 Gene-Disease associations (from GenCC):

achromatopsia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
ATF6-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
achromatopsia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-161784051-G-A is Benign according to our data. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161784051-G-A is described in CliVar as Benign. Clinvar id is 1164405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.513 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF6	NM_007348.4 link	c.309G>A	p.Ser103Ser	synonymous_variant	Exon 4 of 16	ENST00000367942.4	NP_031374.2	P18850A8K383

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4 link	c.309G>A	p.Ser103Ser	synonymous_variant	Exon 4 of 16	1	NM_007348.4	ENSP00000356919.3		P18850

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18002

AN:

151902

Hom.:

1603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.0934

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.150

AC:

37630

AN:

251124

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.0985

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.0702

Gnomad NFE exome

AF:

0.0722

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.0914

AC:

133245

AN:

1458354

Hom.:

11144

Cov.:

AF XY:

0.0898

AC XY:

65134

AN XY:

725702

show subpopulations

African (AFR)

AF:

0.133

AC:

4449

AN:

33410

American (AMR)

AF:

0.432

AC:

19305

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2747

AN:

26098

East Asian (EAS)

AF:

0.342

AC:

13531

AN:

39554

South Asian (SAS)

AF:

0.0857

AC:

7387

AN:

86150

European-Finnish (FIN)

AF:

0.0660

AC:

3522

AN:

53384

Middle Eastern (MID)

AF:

0.0955

AC:

550

AN:

5760

European-Non Finnish (NFE)

AF:

0.0682

AC:

75622

AN:

1109082

Other (OTH)

AF:

0.102

AC:

6132

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

5286

10572

15858

21144

26430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3152

6304

9456

12608

15760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.119

AC:

18046

AN:

152020

Hom.:

1618

Cov.:

AF XY:

0.122

AC XY:

9029

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.136

AC:

5631

AN:

41464

American (AMR)

AF:

0.269

AC:

4097

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

350

AN:

3468

East Asian (EAS)

AF:

0.314

AC:

1627

AN:

5174

South Asian (SAS)

AF:

0.0926

AC:

446

AN:

4814

European-Finnish (FIN)

AF:

0.0691

AC:

729

AN:

10552

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0712

AC:

4842

AN:

67984

Other (OTH)

AF:

0.128

AC:

270

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

739

1477

2216

2954

3693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

1245

Bravo

AF:

0.140

Asia WGS

AF:

0.255

AC:

889

AN:

3478

EpiCase

AF:

0.0734

EpiControl

AF:

0.0756

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Achromatopsia 7

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.5

(source)

DANN

Benign

0.72

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over