1-161976937-A-G

Variant names:

• chr1-161976937-A-G
• rs2340727
• ENST00000681738.1:n.*1068A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ATF6 Gene-Disease associations (from GenCC):

• achromatopsia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• ATF6-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• achromatopsia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681738.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	ENST00000681738.1		n.*1068A>G		non_coding_transcript_exon	Exon 17 of 17	ENSP00000505025.1
	ATF6	ENST00000681738.1		n.*1068A>G		3_prime_UTR	Exon 17 of 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

African (AFR) AF: 0.745 AC: 30865 AN: 41428

American (AMR) AF: 0.159 AC: 2439 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1271 AN: 5166

South Asian (SAS) AF: 0.187 AC: 902 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1646 AN: 10600

Middle Eastern (MID) AF: 0.172 AC: 50 AN: 290

European-Non Finnish (NFE) AF: 0.158 AC: 10753 AN: 67978

Other (OTH) AF: 0.267 AC: 563 AN: 2112

Alfa AF: 0.213 Hom.: 18944

Bravo AF: 0.337

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.26
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs2340727; hg19: chr1-161946727;