rs924777

Variant names:

• chr1-161879114-G-A
• rs924777
• NM_007348.4:c.1719+15802G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-161879114-G-A
• chr1-161879114-G-C
• chr1-161879114-G-T

Variant summary

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

The NM_007348.4(ATF6):​c.1719+15802G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,146 control chromosomes in the GnomAD database, including 62,100 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 (62100 hom., cov: 31)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF6	NM_007348.4	c.1719+15802G>A		intron_variant	Intron 14 of 15	ENST00000367942.4	NP_031374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4	c.1719+15802G>A		intron_variant	Intron 14 of 15	1	NM_007348.4	ENSP00000356919.3

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137172 AN: 152028 Hom.: 62039 Cov.: 31

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.905

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: 0.902 AC: 137293 AN: 152146 Hom.: 62100 Cov.: 31 AF XY: 0.902 AC XY: 67095 AN XY: 74394

African (AFR) AF: 0.960 AC: 39881 AN: 41528

American (AMR) AF: 0.892 AC: 13622 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3087 AN: 3468

East Asian (EAS) AF: 0.884 AC: 4564 AN: 5162

South Asian (SAS) AF: 0.861 AC: 4149 AN: 4820

European-Finnish (FIN) AF: 0.907 AC: 9629 AN: 10614

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59531 AN: 67958

Other (OTH) AF: 0.905 AC: 1914 AN: 2114

Alfa AF: 0.880 Hom.: 30034

Bravo AF: 0.905

Asia WGS AF: 0.895 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.19
PhyloP100		-0.28
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: rs924777; hg19: chr1-161848904;