Variant chr1-161778266-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000367942.4(ATF6):c.105C>T(p.Leu35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 1,611,804 control chromosomes in the GnomAD database, including 12,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1674 hom., cov: 32)

Exomes 𝑓: 0.092 ( 11220 hom. )

Consequence

ATF6
ENST00000367942.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.192

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-161778266-C-T is Benign according to our data. Variant chr1-161778266-C-T is described in ClinVar as [Benign]. Clinvar id is 1164403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.192 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 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.105C>T	p.Leu35=	synonymous_variant	2/16	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.105C>T	p.Leu35=	synonymous_variant	2/16	1	NM_007348.4	ENSP00000356919	A2

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18456

AN:

152034

Hom.:

1658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.0947

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0713

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.150

AC:

37486

AN:

250430

Hom.:

5480

AF XY:

0.134

AC XY:

18150

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.0980

Gnomad EAS exome

AF:

0.311

Gnomad SAS exome

AF:

0.0861

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0719

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.0922

AC:

134639

AN:

1459652

Hom.:

11220

Cov.:

AF XY:

0.0905

AC XY:

65716

AN XY:

726176

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.0857

Gnomad4 FIN exome

AF:

0.0658

Gnomad4 NFE exome

AF:

0.0690

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.122

AC:

18506

AN:

152152

Hom.:

1674

Cov.:

AF XY:

0.125

AC XY:

9268

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.0939

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0888

Hom.:

1553

Bravo

AF:

0.143

Asia WGS

AF:

0.258

AC:

896

AN:

3478

EpiCase

AF:

0.0732

EpiControl

AF:

0.0757

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

-0.36

CADD

Benign

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)

0.050

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