rs2272296

Variant names:

• chr12-53116149-C-T
• rs2272296
• NM_003578.4:c.761C>T

Variant summary

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

The NM_003578.4(SOAT2):​c.761C>T​(p.Thr254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,142 control chromosomes in the GnomAD database, including 26,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.24 (4836 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21923 hom.)
• Consequence: SOAT2 NM_003578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 32 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]

ENSG00000309140 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030106604).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOAT2	NM_003578.4	c.761C>T	p.Thr254Ile	missense_variant	Exon 7 of 15	ENST00000301466.8	NP_003569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOAT2	ENST00000301466.8	c.761C>T	p.Thr254Ile	missense_variant	Exon 7 of 15	1	NM_003578.4	ENSP00000301466.3
SOAT2	ENST00000542365.1	n.761C>T		non_coding_transcript_exon_variant	Exon 7 of 14	2		ENSP00000442234.1
ENSG00000309140	ENST00000839022.1	n.241+6905G>A		intron_variant	Intron 1 of 1
ENSG00000309140	ENST00000839023.1	n.224+6924G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35761 AN: 152004 Hom.: 4816 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.189 AC: 47544 AN: 251330 AF XY: 0.184

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.163 AC: 237848 AN: 1461020 Hom.: 21923 Cov.: 31 AF XY: 0.162 AC XY: 117884 AN XY: 726876

African (AFR) AF: 0.370 AC: 12373 AN: 33420

American (AMR) AF: 0.167 AC: 7470 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5484 AN: 26122

East Asian (EAS) AF: 0.358 AC: 14213 AN: 39684

South Asian (SAS) AF: 0.126 AC: 10830 AN: 86238

European-Finnish (FIN) AF: 0.219 AC: 11673 AN: 53402

Middle Eastern (MID) AF: 0.204 AC: 1175 AN: 5766

European-Non Finnish (NFE) AF: 0.147 AC: 163888 AN: 1111310

Other (OTH) AF: 0.178 AC: 10742 AN: 60368

GnomAD4 genome AF: 0.235 AC: 35822 AN: 152122 Hom.: 4836 Cov.: 32 AF XY: 0.236 AC XY: 17548 AN XY: 74354

African (AFR) AF: 0.369 AC: 15329 AN: 41490

American (AMR) AF: 0.201 AC: 3066 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1647 AN: 5168

South Asian (SAS) AF: 0.129 AC: 625 AN: 4830

European-Finnish (FIN) AF: 0.227 AC: 2399 AN: 10578

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11164 AN: 67976

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.189 Hom.: 9254

Bravo AF: 0.238

TwinsUK AF: 0.152 AC: 565

ALSPAC AF: 0.127 AC: 488

ESP6500AA AF: 0.351 AC: 1546

ESP6500EA AF: 0.154 AC: 1327

ExAC AF: 0.192 AC: 23331

Asia WGS AF: 0.188 AC: 654 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.5
DANN	Benign	0.60
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.015	N
PhyloP100		0.34
PrimateAI	Benign	0.39	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.081
Sift	Benign	0.42	T
Sift4G	Benign	0.77	T
Polyphen		0.0020	B
Vest4		0.026
MPC		0.14
ClinPred		0.0065	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.12
Mutation Taster		=95/5	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: rs2272296; hg19: chr12-53509933; COSMIC: COSV56859795; COSMIC: COSV56859795;