rs2490429

chr1-161972719-T-C

Variant summary

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

The ENST00000681738.1(ATF6):c.*57-3207T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,282 control chromosomes in the GnomAD database, including 66,046 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 0.93 (66046 hom., cov: 33)
• Consequence: ATF6 ENST00000681738.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.*57-3207T>C		intron_variant, NMD_transcript_variant
ATF6	ENST00000681801.1	c.*57-2467T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141563 AN: 152164 Hom.: 65986 Cov.: 33

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.930 AC: 141682 AN: 152282 Hom.: 66046 Cov.: 33 AF XY: 0.931 AC XY: 69286 AN XY: 74458

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.943

Alfa AF: 0.919 Hom.: 10392

Bravo AF: 0.933

Asia WGS AF: 0.967 AC: 3364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.5
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2490429; hg19: chr1-161942509;