chr1-161879595-A-C

Position:

• chr1-161879595-A-C

Variant summary

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

The NM_007348.4(ATF6):​c.1719+16283A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,900 control chromosomes in the GnomAD database, including 22,497 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 0.49 (22497 hom., cov: 31)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF6	NM_007348.4	c.1719+16283A>C		intron_variant		ENST00000367942.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6	ENST00000367942.4	c.1719+16283A>C		intron_variant		1	NM_007348.4	A2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74915 AN: 151782 Hom.: 22497 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.493 AC: 74910 AN: 151900 Hom.: 22497 Cov.: 31 AF XY: 0.496 AC XY: 36823 AN XY: 74240

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.538

Alfa AF: 0.438 Hom.: 1531

Bravo AF: 0.459

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.57

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: rs2340721; hg19: chr1-161849385;