rs2341481

Variant names:

• chr1-161934708-G-A
• rs2341481
• NM_007348.4:c.1804+22328G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-161934708-G-A
• chr1-161934708-G-C

Variant summary

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

The NM_007348.4(ATF6):​c.1804+22328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,028 control chromosomes in the GnomAD database, including 32,017 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 0.63 (32017 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	NM_007348.4	MANE Select	c.1804+22328G>A		intron	N/A	NP_031374.2
	ATF6	NM_001437597.1		c.1861+22328G>A		intron	N/A	NP_001424526.1
	ATF6	NM_001410890.1		c.1801+22328G>A		intron	N/A	NP_001397819.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	ENST00000367942.4	TSL:1 MANE Select	c.1804+22328G>A		intron	N/A	ENSP00000356919.3
	ATF6	ENST00000681492.1		c.1894+22328G>A		intron	N/A	ENSP00000506139.1
	ATF6	ENST00000680688.1		c.1861+22328G>A		intron	N/A	ENSP00000504865.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95838 AN: 151910 Hom.: 32001 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.631 AC: 95883 AN: 152028 Hom.: 32017 Cov.: 32 AF XY: 0.628 AC XY: 46691 AN XY: 74312

African (AFR) AF: 0.433 AC: 17934 AN: 41414

American (AMR) AF: 0.533 AC: 8141 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2507 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2690 AN: 5176

South Asian (SAS) AF: 0.595 AC: 2872 AN: 4824

European-Finnish (FIN) AF: 0.806 AC: 8521 AN: 10576

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51061 AN: 67980

Other (OTH) AF: 0.637 AC: 1344 AN: 2110

Alfa AF: 0.654 Hom.: 5915

Bravo AF: 0.602

Asia WGS AF: 0.522 AC: 1816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		0.54
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: rs2341481; hg19: chr1-161904498;