1-179341140-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003101.6(SOAT1):c.610C>G(p.Gln204Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,032 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: SOAT1 NM_003101.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.466

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028687716).
• BP6: Variant 1-179341140-C-G is Benign according to our data. Variant chr1-179341140-C-G is described in ClinVar as [Benign]. Clinvar id is 780280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1925/152182) while in subpopulation AFR AF= 0.0443 (1838/41510). AF 95% confidence interval is 0.0426. There are 62 homozygotes in gnomad4. There are 901 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6	c.610C>G	p.Gln204Glu	missense_variant	7/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8	c.610C>G	p.Gln204Glu	missense_variant	7/16	1	NM_003101.6	P1
SOAT1	ENST00000540564.5	c.436C>G	p.Gln146Glu	missense_variant	6/15	1
SOAT1	ENST00000539888.5	c.415C>G	p.Gln139Glu	missense_variant	6/15	2
SOAT1	ENST00000426956.1	c.610C>G	p.Gln204Glu	missense_variant	7/7	3

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1922 AN: 152064 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00312 AC: 783 AN: 251350 Hom.: 22 AF XY: 0.00234 AC XY: 318 AN XY: 135842

Gnomad AFR exome AF: 0.0445

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00117 AC: 1710 AN: 1461850 Hom.: 35 Cov.: 32 AF XY: 0.00102 AC XY: 739 AN XY: 727232

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome AF: 0.0126 AC: 1925 AN: 152182 Hom.: 62 Cov.: 32 AF XY: 0.0121 AC XY: 901 AN XY: 74412

Gnomad4 AFR AF: 0.0443

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00209 Hom.: 7

Bravo AF: 0.0144

ESP6500AA AF: 0.0399 AC: 176

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00393 AC: 477

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	13
Dann	Benign	0.81
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.71	T;T;T;T
MetaRNN	Benign	0.0029	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.29	T;T;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.0010	.;.;B;.
Vest4		0.065
MVP		0.18
MPC		0.18
ClinPred		0.00088	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.48

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: rs73048613; hg19: chr1-179310275;