rs13306731

Variant names:

• chr1-179351443-A-G
• rs13306731
• NM_003101.6:c.1577A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-179351443-A-G
• chr1-179351443-A-T

Variant summary

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

The NM_003101.6(SOAT1):​c.1577A>G​(p.Gln526Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 1,612,870 control chromosomes in the GnomAD database, including 8,912 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (686 hom., cov: 31)
  • Exomes 𝑓: 0.090 (8226 hom.)
• Consequence: SOAT1 NM_003101.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 34 publications found

Genes affected

SOAT1 (HGNC:11177): (sterol O-acyltransferase 1) The protein encoded by this gene belongs to the acyltransferase family. It is located in the endoplasmic reticulum, and catalyzes the formation of fatty acid-cholesterol esters. This gene has been implicated in the formation of beta-amyloid and atherosclerotic plaques by controlling the equilibrium between free cholesterol and cytoplasmic cholesteryl esters. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013990998).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003101.6. 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
	SOAT1	NM_003101.6	MANE Select	c.1577A>G	p.Gln526Arg	missense	Exon 15 of 16	NP_003092.4
	SOAT1	NM_001252511.2		c.1403A>G	p.Gln468Arg	missense	Exon 14 of 15	NP_001239440.1	P35610-2
	SOAT1	NM_001252512.2		c.1382A>G	p.Gln461Arg	missense	Exon 14 of 15	NP_001239441.1	P35610-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOAT1	ENST00000367619.8	TSL:1 MANE Select	c.1577A>G	p.Gln526Arg	missense	Exon 15 of 16	ENSP00000356591.3	P35610-1
	SOAT1	ENST00000540564.5	TSL:1	c.1403A>G	p.Gln468Arg	missense	Exon 14 of 15	ENSP00000445315.1	P35610-2
	SOAT1	ENST00000904814.1		c.1604A>G	p.Gln535Arg	missense	Exon 15 of 16	ENSP00000574873.1

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11236 AN: 152088 Hom.: 687 Cov.: 31

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0631

GnomAD2 exomes AF: 0.112 AC: 28010 AN: 250388 AF XY: 0.111

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.0491

Gnomad EAS exome AF: 0.328

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0730

Gnomad OTH exome AF: 0.0873

GnomAD4 exome AF: 0.0899 AC: 131265 AN: 1460664 Hom.: 8226 Cov.: 31 AF XY: 0.0910 AC XY: 66148 AN XY: 726634

African (AFR) AF: 0.0106 AC: 354 AN: 33388

American (AMR) AF: 0.164 AC: 7282 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 1265 AN: 26090

East Asian (EAS) AF: 0.346 AC: 13729 AN: 39686

South Asian (SAS) AF: 0.148 AC: 12696 AN: 85982

European-Finnish (FIN) AF: 0.0989 AC: 5279 AN: 53388

Middle Eastern (MID) AF: 0.0523 AC: 301 AN: 5760

European-Non Finnish (NFE) AF: 0.0766 AC: 85092 AN: 1111564

Other (OTH) AF: 0.0873 AC: 5267 AN: 60334

GnomAD4 genome AF: 0.0738 AC: 11226 AN: 152206 Hom.: 686 Cov.: 31 AF XY: 0.0790 AC XY: 5875 AN XY: 74396

African (AFR) AF: 0.0142 AC: 592 AN: 41568

American (AMR) AF: 0.108 AC: 1654 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1720 AN: 5172

South Asian (SAS) AF: 0.149 AC: 718 AN: 4816

European-Finnish (FIN) AF: 0.104 AC: 1097 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5067 AN: 67990

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0763 Hom.: 2139

Bravo AF: 0.0723

TwinsUK AF: 0.0801 AC: 297

ALSPAC AF: 0.0737 AC: 284

ESP6500AA AF: 0.0172 AC: 76

ESP6500EA AF: 0.0735 AC: 632

ExAC AF: 0.108 AC: 13072

Asia WGS AF: 0.214 AC: 743 AN: 3478

EpiCase AF: 0.0685

EpiControl AF: 0.0718

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.59
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.12	N
PhyloP100		1.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.057
Sift	Benign	0.93	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.18
ClinPred		0.0083	T
GERP RS		5.6
Varity_R		0.061
gMVP		0.67
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13306731; hg19: chr1-179320578; COSMIC: COSV62652519;