dbSNP rs11579627: ATF6:c.*2510G>A (chr1-161961164-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007348.4(ATF6):c.*2510G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,230 control chromosomes in the GnomAD database, including 3,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3844 hom., cov: 33)

Exomes 𝑓: 0.46 ( 1 hom. )

Consequence

ATF6
NM_007348.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ATF6	NM_007348.4 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16	ENST00000367942.4	NP_031374.2
ATF6	NM_001437597.1 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16		NP_001424526.1
ATF6	NM_001410890.1 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16		NP_001397819.1
ATF6	XM_011509309.1 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16		XP_011507611.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ATF6	ENST00000367942.4 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16	1	NM_007348.4	ENSP00000356919.3
ATF6	ENST00000679853.1 link	c.*2510G>A	3_prime_UTR_variant	Exon 16 of 16			ENSP00000506149.1
ATF6	ENST00000681738.1 link	n.*56+2454G>A	intron_variant	Intron 16 of 16			ENSP00000505025.1
ATF6	ENST00000681801.1 link	n.*56+2454G>A	intron_variant	Intron 16 of 16			ENSP00000505998.1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30542

AN:

152088

Hom.:

3846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.458

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.201

AC:

30533

AN:

152206

Hom.:

3844

Cov.:

AF XY:

0.202

AC XY:

15016

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0513

AC:

2129

AN:

41520

American (AMR)

AF:

0.196

AC:

2990

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

719

AN:

3472

East Asian (EAS)

AF:

0.223

AC:

1152

AN:

5174

South Asian (SAS)

AF:

0.163

AC:

788

AN:

4830

European-Finnish (FIN)

AF:

0.312

AC:

3298

AN:

10586

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18670

AN:

68010

Other (OTH)

AF:

0.204

AC:

431

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1200

2399

3599

4798

5998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.230

Hom.:

1394

Bravo

AF:

0.187

Asia WGS

AF:

0.175

AC:

608

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.49

(source)

DANN

Benign

0.55

PhyloP100

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over