rs2340727

Positions:

• chr1-161976937-A-G

Variant summary

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

The ENST00000681738.1(ATF6):​n.*1068A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,072 control chromosomes in the GnomAD database, including 13,144 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 0.32 (13144 hom., cov: 32)
• Consequence: ATF6 ENST00000681738.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.161976937A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000681738.1	n.*1068A>G		non_coding_transcript_exon_variant	17/17			ENSP00000505025.1
ATF6	ENST00000681738.1	n.*1068A>G		3_prime_UTR_variant	17/17			ENSP00000505025.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48851 AN: 151954 Hom.: 13107 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.322 AC: 48939 AN: 152072 Hom.: 13144 Cov.: 32 AF XY: 0.316 AC XY: 23528 AN XY: 74352

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.267

Alfa AF: 0.181 Hom.: 5325

Bravo AF: 0.337

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2340727; hg19: chr1-161946727;