rs9658625

Variant names:

• chr12-53103618-A-G
• rs9658625
• NM_003578.4:c.41A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.076 (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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003578.4. 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
	SOAT2	NM_003578.4	MANE Select	c.41A>G	p.Glu14Gly	missense	Exon 1 of 15	NP_003569.1	O75908-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOAT2	ENST00000301466.8	TSL:1 MANE Select	c.41A>G	p.Glu14Gly	missense	Exon 1 of 15	ENSP00000301466.3	O75908-1
	SOAT2	ENST00000869113.1		c.41A>G	p.Glu14Gly	missense	Exon 1 of 15	ENSP00000539172.1
	SOAT2	ENST00000869112.1		c.41A>G	p.Glu14Gly	missense	Exon 1 of 14	ENSP00000539171.1

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

GnomAD2 exomes AF: 0.0935 AC: 13238 AN: 141642 AF XY: 0.0950

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 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

African (AFR) AF: 0.0477 AC: 1503 AN: 31538

American (AMR) AF: 0.126 AC: 4449 AN: 35414

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 2336 AN: 25072

East Asian (EAS) AF: 0.191 AC: 6812 AN: 35724

South Asian (SAS) AF: 0.115 AC: 9080 AN: 79086

European-Finnish (FIN) AF: 0.0735 AC: 3295 AN: 44850

Middle Eastern (MID) AF: 0.129 AC: 727 AN: 5646

European-Non Finnish (NFE) AF: 0.0653 AC: 70363 AN: 1078322

Other (OTH) AF: 0.0817 AC: 4729 AN: 57900

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

African (AFR) AF: 0.0483 AC: 2005 AN: 41530

American (AMR) AF: 0.130 AC: 1982 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3468

East Asian (EAS) AF: 0.160 AC: 824 AN: 5144

South Asian (SAS) AF: 0.122 AC: 588 AN: 4828

European-Finnish (FIN) AF: 0.0819 AC: 868 AN: 10600

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4693 AN: 67974

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0743 Hom.: 1536

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 v4.9

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
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.66
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.043
Sift	Benign	0.11	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.050
MPC		0.15
ClinPred		0.018	T
GERP RS		1.2
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.41
Mutation Taster		=97/3	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: rs9658625; hg19: chr12-53497402; COSMIC: COSV56857138; COSMIC: COSV56857138;