rs12079579

Positions:

• chr1-161910692-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007348.4(ATF6):​c.1720-1604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,066 control chromosomes in the GnomAD database, including 2,196 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 0.14 (2196 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF6	NM_007348.4	c.1720-1604G>A		intron_variant		ENST00000367942.4	NP_031374.2
ATF6	NM_001410890.1	c.1717-1604G>A		intron_variant			NP_001397819.1
ATF6	XM_011509308.1	c.1777-1604G>A		intron_variant			XP_011507610.1
ATF6	XM_011509309.1	c.1774-1604G>A		intron_variant			XP_011507611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4	c.1720-1604G>A		intron_variant		1	NM_007348.4	ENSP00000356919	A2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21309 AN: 151948 Hom.: 2183 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.140 AC: 21354 AN: 152066 Hom.: 2196 Cov.: 32 AF XY: 0.136 AC XY: 10112 AN XY: 74338

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.0637

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0993 Hom.: 436

Bravo AF: 0.145

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs12079579; hg19: chr1-161880482;