1-179342967-T-C

Position:

• chr1-179342967-T-C

Variant summary

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

The NM_003101.6(SOAT1):​c.941+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,588,346 control chromosomes in the GnomAD database, including 188,958 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 0.46 (16034 hom., cov: 31)
  • Exomes 𝑓: 0.49 (172924 hom.)
• Consequence: SOAT1 NM_003101.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOAT1	NM_003101.6	c.941+24T>C		intron_variant		ENST00000367619.8	NP_003092.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOAT1	ENST00000367619.8	c.941+24T>C		intron_variant		1	NM_003101.6	ENSP00000356591	P1
SOAT1	ENST00000540564.5	c.767+24T>C		intron_variant		1		ENSP00000445315
SOAT1	ENST00000539888.5	c.746+24T>C		intron_variant		2		ENSP00000441356

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69467 AN: 151820 Hom.: 16026 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.467

GnomAD3 exomes AF: 0.461 AC: 115858 AN: 251142 Hom.: 27036 AF XY: 0.464 AC XY: 62978 AN XY: 135754

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.477

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.489 AC: 702143 AN: 1436406 Hom.: 172924 Cov.: 25 AF XY: 0.487 AC XY: 349031 AN XY: 716352

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.458 AC: 69524 AN: 151940 Hom.: 16034 Cov.: 31 AF XY: 0.454 AC XY: 33685 AN XY: 74252

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.471

Alfa AF: 0.491 Hom.: 39070

Bravo AF: 0.454

Asia WGS AF: 0.462 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4651024; hg19: chr1-179312102; COSMIC: COSV62653284; COSMIC: COSV62653284;