1-161771484-T-C

Variant summary

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

The NM_007348.4(ATF6):c.82+5042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,132 control chromosomes in the GnomAD database, including 22,502 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 0.49 (22502 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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]

LOC124904444 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF6	NM_007348.4	c.82+5042T>C		intron_variant		ENST00000367942.4
LOC124904444	XR_007066695.1	n.2815T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6	ENST00000367942.4	c.82+5042T>C		intron_variant		1	NM_007348.4	A2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74770 AN: 152014 Hom.: 22502 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.491 AC: 74760 AN: 152132 Hom.: 22502 Cov.: 32 AF XY: 0.494 AC XY: 36768 AN XY: 74360

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.537

Alfa AF: 0.634 Hom.: 60247

Bravo AF: 0.457

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.7
Dann	Benign	0.31

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: rs905594; hg19: chr1-161741274; COSMIC: COSV63406395;