rs9658625

Positions:

• chr12-53103618-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003578.4(SOAT2):​c.41A>G​(p.Glu14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 1,545,708 control chromosomes in the GnomAD database, including 4,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.076 (519 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4374 hom.)
• Consequence: SOAT2 NM_003578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

Genes affected

SOAT2 (HGNC:11178): (sterol O-acyltransferase 2) Summary:This gene is a member of a small family of acyl coenzyme A:cholesterol acyltransferases. The gene encodes a membrane-bound enzyme localized in the endoplasmic reticulum that produces intracellular cholesterol esters from long-chain fatty acyl CoA and cholesterol. The cholesterol esters are then stored as cytoplasmic lipid droplets inside the cell. The enzyme is implicated in cholesterol absorption in the intestine and in the assembly and secretion of apolipoprotein B-containing lipoproteins such as very low density lipoprotein (VLDL). Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014986098).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT2	NM_003578.4	c.41A>G	p.Glu14Gly	missense_variant	1/15	ENST00000301466.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT2	ENST00000301466.8	c.41A>G	p.Glu14Gly	missense_variant	1/15	1	NM_003578.4	P1
SOAT2	ENST00000551896.5	c.41A>G	p.Glu14Gly	missense_variant	1/5	2
SOAT2	ENST00000542365.1	c.41A>G	p.Glu14Gly	missense_variant, NMD_transcript_variant	1/14	2

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11632 AN: 152038 Hom.: 519 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0946

GnomAD3 exomes AF: 0.0935 AC: 13238 AN: 141642 Hom.: 712 AF XY: 0.0950 AC XY: 7191 AN XY: 75656

Gnomad AFR exome AF: 0.0456

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0970

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0764

Gnomad NFE exome AF: 0.0694

Gnomad OTH exome AF: 0.0936

GnomAD4 exome AF: 0.0741 AC: 103294 AN: 1393552 Hom.: 4374 Cov.: 32 AF XY: 0.0756 AC XY: 51995 AN XY: 687584

Gnomad4 AFR exome AF: 0.0477

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0932

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0735

Gnomad4 NFE exome AF: 0.0653

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0765 AC: 11639 AN: 152156 Hom.: 519 Cov.: 32 AF XY: 0.0798 AC XY: 5937 AN XY: 74390

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0946

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0747 Hom.: 1123

Bravo AF: 0.0776

TwinsUK AF: 0.0634 AC: 235

ALSPAC AF: 0.0573 AC: 221

ESP6500AA AF: 0.0410 AC: 152

ESP6500EA AF: 0.0592 AC: 415

ExAC AF: 0.0591 AC: 2432

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.98
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.89	P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.043
Sift	Benign	0.11	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0010	.;B
Vest4		0.050
MPC		0.15
ClinPred		0.018	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.41

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: rs9658625; hg19: chr12-53497402; COSMIC: COSV56857138; COSMIC: COSV56857138;