Variant 1-161784012-T-C 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.270T>C(p.Pro90Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,609,026 control chromosomes in the GnomAD database, including 11,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 1268 hom., cov: 31)

Exomes 𝑓: 0.089 ( 10690 hom. )

Consequence

ATF6
NM_007348.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.840

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=-0.54).

BP6

Variant 1-161784012-T-C is Benign according to our data. Variant chr1-161784012-T-C is described in ClinVar as [Benign]. Clinvar id is 1164404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.84 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 link	c.270T>C	p.Pro90Pro	synonymous_variant	4/16	ENST00000367942.4	NP_031374.2	P18850A8K383

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4 link	c.270T>C	p.Pro90Pro	synonymous_variant	4/16	1	NM_007348.4	ENSP00000356919.3		P18850

Frequencies

GnomAD3 genomes

AF:

0.0964

AC:

14660

AN:

152048

Hom.:

1255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0711

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.144

AC:

36112

AN:

251158

Hom.:

5341

AF XY:

0.130

AC XY:

17653

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.0551

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.0984

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.0865

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.0719

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0886

AC:

129147

AN:

1456860

Hom.:

10690

Cov.:

AF XY:

0.0874

AC XY:

63391

AN XY:

725016

show subpopulations

Gnomad4 AFR exome

AF:

0.0568

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.0853

Gnomad4 FIN exome

AF:

0.0658

Gnomad4 NFE exome

AF:

0.0675

Gnomad4 OTH exome

AF:

0.0954

GnomAD4 genome

AF:

0.0966

AC:

14693

AN:

152166

Hom.:

1268

Cov.:

AF XY:

0.100

AC XY:

7457

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0582

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.0921

Gnomad4 FIN

AF:

0.0684

Gnomad4 NFE

AF:

0.0711

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0794

Hom.:

685

Bravo

AF:

0.115

Asia WGS

AF:

0.247

AC:

860

AN:

3478

EpiCase

AF:

0.0732

EpiControl

AF:

0.0753

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.54

CADD

Benign

9.7

DANN

Benign

0.79

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