rs1962508

chr1-161975629-C-Achr1-161975629-C-T

Variant summary

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

The ENST00000681738.1(ATF6):c.*57-297C>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,072 control chromosomes in the GnomAD database, including 19,806 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 0.45 (19806 hom., cov: 32)
• Consequence: ATF6 ENST00000681738.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6	ENST00000681738.1	c.*57-297C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67814 AN: 151954 Hom.: 19744 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.447 AC: 67946 AN: 152072 Hom.: 19806 Cov.: 32 AF XY: 0.446 AC XY: 33143 AN XY: 74354

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.412

Alfa AF: 0.362 Hom.: 3860

Bravo AF: 0.478

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.11
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1962508; hg19: chr1-161945419;