rs4532807

Positions:

• chr1-161887406-A-G

Variant summary

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

The NM_007348.4(ATF6):​c.1719+24094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,126 control chromosomes in the GnomAD database, including 1,898 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 0.11 (1898 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF6	NM_007348.4	c.1719+24094A>G		intron_variant		ENST00000367942.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6	ENST00000367942.4	c.1719+24094A>G		intron_variant		1	NM_007348.4	A2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16882 AN: 152006 Hom.: 1893 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16904 AN: 152126 Hom.: 1898 Cov.: 32 AF XY: 0.111 AC XY: 8250 AN XY: 74406

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.0383

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0600 Hom.: 265

Bravo AF: 0.120

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4532807; hg19: chr1-161857196;