rs3753526

Positions:

• chr1-179350406-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003101.6(SOAT1):​c.1425C>G​(p.Leu475Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,612,522 control chromosomes in the GnomAD database, including 11,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (1083 hom., cov: 33)
  • Exomes 𝑓: 0.096 (10120 hom.)
• Consequence: SOAT1 NM_003101.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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]

SOAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.241 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOAT1	NM_003101.6	c.1425C>G	p.Leu475Leu	synonymous_variant	14/16	ENST00000367619.8	NP_003092.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOAT1	ENST00000367619.8	c.1425C>G	p.Leu475Leu	synonymous_variant	14/16	1	NM_003101.6	ENSP00000356591.3
SOAT1	ENST00000540564.5	c.1251C>G	p.Leu417Leu	synonymous_variant	13/15	1		ENSP00000445315.1
SOAT1	ENST00000539888.5	c.1230C>G	p.Leu410Leu	synonymous_variant	13/15	2		ENSP00000441356.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15083 AN: 151992 Hom.: 1084 Cov.: 33

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0882

GnomAD3 exomes AF: 0.134 AC: 33580 AN: 251326 Hom.: 3447 AF XY: 0.129 AC XY: 17459 AN XY: 135844

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.378

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0733

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0964 AC: 140815 AN: 1460412 Hom.: 10120 Cov.: 32 AF XY: 0.0973 AC XY: 70712 AN XY: 726598

Gnomad4 AFR exome AF: 0.0711

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.0483

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.0992

Gnomad4 NFE exome AF: 0.0765

Gnomad4 OTH exome AF: 0.0984

GnomAD4 genome AF: 0.0992 AC: 15088 AN: 152110 Hom.: 1083 Cov.: 33 AF XY: 0.105 AC XY: 7832 AN XY: 74342

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0788 Hom.: 198

Bravo AF: 0.104

Asia WGS AF: 0.263 AC: 913 AN: 3478

EpiCase AF: 0.0689

EpiControl AF: 0.0724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3753526; hg19: chr1-179319541; COSMIC: COSV62657184;