1-179342188-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_003101.6(SOAT1):c.855A>G(p.Lys285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 1,610,500 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (44 hom.)
• Consequence: SOAT1 NM_003101.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.402

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-179342188-A-G is Benign according to our data. Variant chr1-179342188-A-G is described in ClinVar as [Benign]. Clinvar id is 773819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.402 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6	c.855A>G	p.Lys285=	synonymous_variant	8/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8	c.855A>G	p.Lys285=	synonymous_variant	8/16	1	NM_003101.6	P1
SOAT1	ENST00000540564.5	c.681A>G	p.Lys227=	synonymous_variant	7/15	1
SOAT1	ENST00000539888.5	c.660A>G	p.Lys220=	synonymous_variant	7/15	2

Frequencies

GnomAD3 genomes AF: 0.00469 AC: 713 AN: 151998 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00755

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00684

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00560 AC: 1403 AN: 250348 Hom.: 4 AF XY: 0.00587 AC XY: 795 AN XY: 135414

Gnomad AFR exome AF: 0.000805

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00245

Gnomad FIN exome AF: 0.00804

Gnomad NFE exome AF: 0.00789

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00653 AC: 9521 AN: 1458384 Hom.: 44 Cov.: 30 AF XY: 0.00651 AC XY: 4721 AN XY: 725664

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00706

Gnomad4 NFE exome AF: 0.00718

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.00469 AC: 713 AN: 152116 Hom.: 5 Cov.: 31 AF XY: 0.00507 AC XY: 377 AN XY: 74364

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00755

Gnomad4 NFE AF: 0.00684

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00655 Hom.: 1

Bravo AF: 0.00427

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

May 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	5.5
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs144255785; hg19: chr1-179311323; COSMIC: COSV62654652; COSMIC: COSV62654652;