12-124800202-A-G

Variant names:

• chr12-124800202-A-G
• rs5888
• NM_005505.5:c.1050T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005505.5(SCARB1):​c.1050T>C​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,832 control chromosomes in the GnomAD database, including 248,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31231 hom., cov: 32)
  • Exomes 𝑓: 0.54 (217210 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.31

Genes affected

SCARB1 (HGNC:1664): (scavenger receptor class B member 1) The protein encoded by this gene is a plasma membrane receptor for high density lipoprotein cholesterol (HDL). The encoded protein mediates cholesterol transfer to and from HDL. In addition, this protein is a receptor for hepatitis C virus glycoprotein E2 and facilitates cell entry by the virus, SARS-CoV2. [provided by RefSeq, Oct 2021]

ENSG00000287242 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-124800202-A-G is Benign according to our data. Variant chr12-124800202-A-G is described in ClinVar as [Benign]. Clinvar id is 1236346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124800202-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-6.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1050T>C	p.Ala350Ala	synonymous_variant	Exon 8 of 13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1050T>C	p.Ala350Ala	synonymous_variant	Exon 8 of 13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95273 AN: 151928 Hom.: 31181 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.605

GnomAD3 exomes AF: 0.588 AC: 147686 AN: 251150 Hom.: 44658 AF XY: 0.576 AC XY: 78145 AN XY: 135746

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.541 AC: 789584 AN: 1460786 Hom.: 217210 Cov.: 42 AF XY: 0.538 AC XY: 391323 AN XY: 726740

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.627 AC: 95381 AN: 152046 Hom.: 31231 Cov.: 32 AF XY: 0.630 AC XY: 46829 AN XY: 74336

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.603

Alfa AF: 0.528 Hom.: 24928

Bravo AF: 0.640

Asia WGS AF: 0.638 AC: 2218 AN: 3478

EpiCase AF: 0.519

EpiControl AF: 0.518

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27651445, 23510561, 28008009, 12519372, 19806217, 17476110, 10397692, 20060115) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

SCARB1-related disorder Benign:1

Mar 13, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.018
DANN	Benign	0.38

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: rs5888; hg19: chr12-125284748; COSMIC: COSV55550544;