Variant rs2271012 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007348.4(ATF6):c.309G>A(p.Ser103=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
ATF6	NM_007348.4 linkuse as main transcript	c.309G>A	p.Ser103=	synonymous_variant	4/16	ENST00000367942.4	NP_031374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4 linkuse as main transcript	c.309G>A	p.Ser103=	synonymous_variant	4/16	1	NM_007348.4	ENSP00000356919	A2

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

GnomAD3 exomes

AF:

0.150

AC:

37630

AN:

251124

Hom.:

5532

AF XY:

0.134

AC XY:

18216

AN XY:

135730

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 SAS exome

AF:

0.0868

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

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.0857

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0682

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.119

AC:

18046

AN:

152020

Hom.:

1618

Cov.:

AF XY:

0.122

AC XY:

9029

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.0926

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0712

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.101

Hom.:

933

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Achromatopsia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.5

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over