1-161811189-G-A

Position:

• chr1-161811189-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.910-8444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,102 control chromosomes in the GnomAD database, including 33,235 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 (33235 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF6	NM_007348.4	c.910-8444G>A		intron_variant		ENST00000367942.4	NP_031374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000367942.4	c.910-8444G>A		intron_variant		1	NM_007348.4	ENSP00000356919	A2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96470 AN: 151984 Hom.: 33214 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.635 AC: 96523 AN: 152102 Hom.: 33235 Cov.: 32 AF XY: 0.639 AC XY: 47495 AN XY: 74358

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.688

Alfa AF: 0.735 Hom.: 83119

Bravo AF: 0.623

Asia WGS AF: 0.696 AC: 2419 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.80

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: rs2134697; hg19: chr1-161780979;