rs13306731

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6	c.1577A>G	p.Gln526Arg	missense_variant	15/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8	c.1577A>G	p.Gln526Arg	missense_variant	15/16	1	NM_003101.6	P1
SOAT1	ENST00000540564.5	c.1403A>G	p.Gln468Arg	missense_variant	14/15	1
SOAT1	ENST00000539888.5	c.1382A>G	p.Gln461Arg	missense_variant	14/15	2

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

GnomAD3 exomes AF: 0.112 AC: 28010 AN: 250388 Hom.: 2367 AF XY: 0.111 AC XY: 14995 AN XY: 135280

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 SAS exome AF: 0.148

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

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.0485

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.0989

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0873

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

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0782 Hom.: 1575

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 v4.3

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
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.51	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.16	P;P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.090	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.93	T;T;T
Sift4G	Benign	0.79	T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306731; hg19: chr1-179320578; COSMIC: COSV62652519;