rs2341475

Variant names:

• chr1-161908818-A-G
• rs2341475
• NM_007348.4:c.1720-3478A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-161908818-A-G
• chr1-161908818-A-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.1720-3478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,044 control chromosomes in the GnomAD database, including 36,082 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 0.66 (36082 hom., cov: 31)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• ATF6-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• achromatopsia

  Inheritance: Unknown, AR Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	NM_007348.4	MANE Select	c.1720-3478A>G		intron	N/A	NP_031374.2	P18850
	ATF6	NM_001437597.1		c.1777-3478A>G		intron	N/A	NP_001424526.1	A0A7P0Z421
	ATF6	NM_001410890.1		c.1717-3478A>G		intron	N/A	NP_001397819.1	A0A7P0TAF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	ENST00000367942.4	TSL:1 MANE Select	c.1720-3478A>G		intron	N/A	ENSP00000356919.3	P18850
	ATF6	ENST00000681492.1		c.1810-3478A>G		intron	N/A	ENSP00000506139.1	A0A7P0TAH1
	ATF6	ENST00000951832.1		c.1807-3478A>G		intron	N/A	ENSP00000621891.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100475 AN: 151926 Hom.: 36066 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.661 AC: 100527 AN: 152044 Hom.: 36082 Cov.: 31 AF XY: 0.665 AC XY: 49444 AN XY: 74336

African (AFR) AF: 0.358 AC: 14818 AN: 41442

American (AMR) AF: 0.792 AC: 12109 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3322 AN: 5172

South Asian (SAS) AF: 0.700 AC: 3376 AN: 4820

European-Finnish (FIN) AF: 0.806 AC: 8518 AN: 10572

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53052 AN: 67970

Other (OTH) AF: 0.726 AC: 1534 AN: 2112

Alfa AF: 0.598 Hom.: 2008

Bravo AF: 0.651

Asia WGS AF: 0.704 AC: 2445 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.37
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: rs2341475; hg19: chr1-161878608;