chr1-161972719-T-C

Variant names:

• chr1-161972719-T-C
• rs2490429
• ENST00000681738.1:n.*57-3207T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000681738.1(ATF6):​n.*57-3207T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 3 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=-0.91).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF6	ENST00000681738.1	n.*57-3207T>C		intron_variant	Intron 16 of 16			ENSP00000505025.1
ATF6	ENST00000681801.1	n.*57-2467T>C		intron_variant	Intron 16 of 16			ENSP00000505998.1

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

African (AFR) AF: 0.969 AC: 40301 AN: 41578

American (AMR) AF: 0.931 AC: 14248 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3284 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5170

South Asian (SAS) AF: 0.923 AC: 4452 AN: 4822

European-Finnish (FIN) AF: 0.914 AC: 9697 AN: 10606

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61621 AN: 68006

Other (OTH) AF: 0.943 AC: 1993 AN: 2114

Alfa AF: 0.921 Hom.: 10753

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
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs2490429; hg19: chr1-161942509;