rs1136046

Variant names:

• chr1-161958981-G-A
• rs1136046
• NM_007348.4:c.*327G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-161958981-G-A
• chr1-161958981-G-T

Variant summary

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

The NM_007348.4(ATF6):​c.*327G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 201,226 control chromosomes in the GnomAD database, including 6,151 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 0.22 (4965 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1186 hom.)
• Consequence: ATF6 NM_007348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 15 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 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.*327G>A		3_prime_UTR	Exon 16 of 16	NP_031374.2	P18850
	ATF6	NM_001437597.1		c.*327G>A		3_prime_UTR	Exon 16 of 16	NP_001424526.1	A0A7P0Z421
	ATF6	NM_001410890.1		c.*327G>A		3_prime_UTR	Exon 16 of 16	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.*327G>A		3_prime_UTR	Exon 16 of 16	ENSP00000356919.3	P18850
	ATF6	ENST00000681492.1		c.*327G>A		3_prime_UTR	Exon 17 of 17	ENSP00000506139.1	A0A7P0TAH1
	ATF6	ENST00000951832.1		c.*327G>A		3_prime_UTR	Exon 17 of 17	ENSP00000621891.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33052 AN: 151860 Hom.: 4950 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.182 AC: 8948 AN: 49248 Hom.: 1186 Cov.: 0 AF XY: 0.179 AC XY: 4478 AN XY: 25052

African (AFR) AF: 0.386 AC: 769 AN: 1992

American (AMR) AF: 0.420 AC: 1128 AN: 2686

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 398 AN: 2096

East Asian (EAS) AF: 0.448 AC: 1701 AN: 3798

South Asian (SAS) AF: 0.242 AC: 291 AN: 1200

European-Finnish (FIN) AF: 0.102 AC: 206 AN: 2022

Middle Eastern (MID) AF: 0.170 AC: 47 AN: 276

European-Non Finnish (NFE) AF: 0.119 AC: 3781 AN: 31792

Other (OTH) AF: 0.185 AC: 627 AN: 3386

GnomAD4 genome AF: 0.218 AC: 33102 AN: 151978 Hom.: 4965 Cov.: 32 AF XY: 0.222 AC XY: 16527 AN XY: 74304

African (AFR) AF: 0.373 AC: 15447 AN: 41410

American (AMR) AF: 0.335 AC: 5127 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1877 AN: 5168

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4814

European-Finnish (FIN) AF: 0.0981 AC: 1036 AN: 10558

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7301 AN: 67954

Other (OTH) AF: 0.224 AC: 474 AN: 2114

Alfa AF: 0.159 Hom.: 4942

Bravo AF: 0.244

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.61
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs1136046; hg19: chr1-161928771;