Variant 12-53103618-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.657

Variant links:

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]

SOAT2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SOAT2	NM_003578.4 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant	1/15	ENST00000301466.8	NP_003569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOAT2	ENST00000301466.8 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant	1/15	1	NM_003578.4	ENSP00000301466	P1	O75908-1
SOAT2	ENST00000551896.5 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant	1/5	2		ENSP00000450120
SOAT2	ENST00000542365.1 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant, NMD_transcript_variant	1/14	2		ENSP00000442234		O75908-4

Frequencies

GnomAD3 genomes

AF:

0.0765

AC:

11632

AN:

152038

Hom.:

519

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0756

AC XY:

51995

AN XY:

687584

show subpopulations

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.:

AF XY:

0.0798

AC XY:

5937

AN XY:

74390

show subpopulations

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

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

0.89

PrimateAI

Benign

0.37

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over