rs12079579

Variant names:

• chr1-161910692-G-A
• rs12079579
• NM_007348.4:c.1720-1604G>A

Variant summary

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

The NM_007348.4(ATF6):​c.1720-1604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,066 control chromosomes in the GnomAD database, including 2,196 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 0.14 (2196 hom., cov: 32)
• Consequence: ATF6 NM_007348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 6 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: G2P, Labcorp Genetics (formerly Invitae)
• ATF6-related retinopathy

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

  Inheritance: Unknown, AR Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	NM_007348.4	MANE Select	c.1720-1604G>A		intron	N/A	NP_031374.2	P18850
	ATF6	NM_001437597.1		c.1777-1604G>A		intron	N/A	NP_001424526.1	A0A7P0Z421
	ATF6	NM_001410890.1		c.1717-1604G>A		intron	N/A	NP_001397819.1	A0A7P0TAF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6	ENST00000367942.4	TSL:1 MANE Select	c.1720-1604G>A		intron	N/A	ENSP00000356919.3	P18850
	ATF6	ENST00000681492.1		c.1810-1604G>A		intron	N/A	ENSP00000506139.1	A0A7P0TAH1
	ATF6	ENST00000951832.1		c.1807-1604G>A		intron	N/A	ENSP00000621891.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21309 AN: 151948 Hom.: 2183 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.140 AC: 21354 AN: 152066 Hom.: 2196 Cov.: 32 AF XY: 0.136 AC XY: 10112 AN XY: 74338

African (AFR) AF: 0.283 AC: 11712 AN: 41432

American (AMR) AF: 0.0637 AC: 974 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1046 AN: 5170

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4828

European-Finnish (FIN) AF: 0.0842 AC: 890 AN: 10566

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0895 AC: 6085 AN: 67986

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0982 Hom.: 479

Bravo AF: 0.145

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.35
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12079579; hg19: chr1-161880482;