rs2499855

chr1-161959971-C-T

Variant summary

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

The NM_007348.4(ATF6):c.*1317C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,240 control chromosomes in the GnomAD database, including 62,117 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 0.90 (62117 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ATF6 NM_007348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF6	NM_007348.4	c.*1317C>T		3_prime_UTR_variant	16/16	ENST00000367942.4
ATF6	NM_001410890.1	c.*1317C>T		3_prime_UTR_variant	16/16
ATF6	XM_011509308.1	c.*1317C>T		3_prime_UTR_variant	16/16
ATF6	XM_011509309.1	c.*1317C>T		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6	ENST00000367942.4	c.*1317C>T		3_prime_UTR_variant	16/16	1	NM_007348.4	A2
ATF6	ENST00000679853.1	c.*1317C>T		3_prime_UTR_variant	16/16			A2
ATF6	ENST00000681738.1	c.*56+1261C>T		intron_variant, NMD_transcript_variant
ATF6	ENST00000681801.1	c.*56+1261C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137231 AN: 152122 Hom.: 62054 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.903

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.902 AC: 137354 AN: 152240 Hom.: 62117 Cov.: 31 AF XY: 0.902 AC XY: 67104 AN XY: 74434

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.903

Alfa AF: 0.883 Hom.: 13740

Bravo AF: 0.904

Asia WGS AF: 0.895 AC: 3113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.70
Dann	Benign	0.47

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: rs2499855; hg19: chr1-161929761;