rs3767633

Variant names:

• chr1-161856825-T-A
• rs3767633
• NM_007348.4:c.1534-3382T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-161856825-T-A
• chr1-161856825-T-C
• chr1-161856825-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007348.4(ATF6):​c.1534-3382T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,254 control chromosomes in the GnomAD database, including 62,356 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 0.90 (62356 hom., cov: 31)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF6	NM_007348.4	c.1534-3382T>A		intron_variant	Intron 12 of 15	ENST00000367942.4	NP_031374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4	c.1534-3382T>A		intron_variant	Intron 12 of 15	1	NM_007348.4	ENSP00000356919.3

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137484 AN: 152136 Hom.: 62290 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.904 AC: 137610 AN: 152254 Hom.: 62356 Cov.: 31 AF XY: 0.903 AC XY: 67239 AN XY: 74430

African (AFR) AF: 0.966 AC: 40133 AN: 41550

American (AMR) AF: 0.892 AC: 13645 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3088 AN: 3468

East Asian (EAS) AF: 0.884 AC: 4574 AN: 5176

South Asian (SAS) AF: 0.862 AC: 4154 AN: 4820

European-Finnish (FIN) AF: 0.907 AC: 9613 AN: 10594

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59569 AN: 68026

Other (OTH) AF: 0.905 AC: 1916 AN: 2116

Alfa AF: 0.892 Hom.: 7515

Bravo AF: 0.906

Asia WGS AF: 0.898 AC: 3126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.69
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3767633; hg19: chr1-161826615;