NM_007348.4:c.*2510G>A

Variant names:

• chr1-161961164-G-A
• rs11579627
• NM_007348.4:c.*2510G>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.*2510G>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 0.201 in 152,230 control chromosomes in the GnomAD database, including 3,845 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 0.20 (3844 hom., cov: 33)
  • Exomes 𝑓: 0.46 (1 hom.)
• Consequence: ATF6 NM_007348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 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.*2510G>A		3_prime_UTR	Exon 16 of 16	NP_031374.2	P18850
	ATF6	NM_001437597.1		c.*2510G>A		3_prime_UTR	Exon 16 of 16	NP_001424526.1	A0A7P0Z421
	ATF6	NM_001410890.1		c.*2510G>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.*2510G>A		3_prime_UTR	Exon 16 of 16	ENSP00000356919.3	P18850
	ATF6	ENST00000679853.1		c.*2510G>A		3_prime_UTR	Exon 16 of 16	ENSP00000506149.1	A0A7P0TAF2
	ATF6	ENST00000681738.1		n.*56+2454G>A		intron	N/A	ENSP00000505025.1	P18850

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30542 AN: 152088 Hom.: 3846 Cov.: 33

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.458 AC: 11 AN: 24 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 7 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 6 AN: 16

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.201 AC: 30533 AN: 152206 Hom.: 3844 Cov.: 33 AF XY: 0.202 AC XY: 15016 AN XY: 74404

African (AFR) AF: 0.0513 AC: 2129 AN: 41520

American (AMR) AF: 0.196 AC: 2990 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1152 AN: 5174

South Asian (SAS) AF: 0.163 AC: 788 AN: 4830

European-Finnish (FIN) AF: 0.312 AC: 3298 AN: 10586

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18670 AN: 68010

Other (OTH) AF: 0.204 AC: 431 AN: 2116

Alfa AF: 0.230 Hom.: 1394

Bravo AF: 0.187

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.55
PhyloP100		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11579627; hg19: chr1-161930954;