rs838897

chr12-124786544-G-Cchr12-124786544-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005505.5(SCARB1):c.1255-41C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,610,992 control chromosomes in the GnomAD database, including 14,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3770 hom., cov: 33)
  • Exomes 𝑓: 0.073 (10325 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-124786544-G-C is Benign according to our data. Variant chr12-124786544-G-C is described in ClinVar as [Benign]. Clinvar id is 1232985.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-124786544-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.1255-41C>G		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.1255-41C>G		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25122 AN: 152122 Hom.: 3740 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.138 AC: 33822 AN: 245882 Hom.: 4715 AF XY: 0.122 AC XY: 16224 AN XY: 133304

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.0747

Gnomad EAS exome AF: 0.436

Gnomad SAS exome AF: 0.0826

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0450

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0732 AC: 106831 AN: 1458752 Hom.: 10325 Cov.: 32 AF XY: 0.0719 AC XY: 52177 AN XY: 725670

Gnomad4 AFR exome AF: 0.372

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.0759

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.0839

Gnomad4 FIN exome AF: 0.0565

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.166 AC: 25207 AN: 152240 Hom.: 3770 Cov.: 33 AF XY: 0.167 AC XY: 12408 AN XY: 74448

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.0991

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.148

Alfa AF: 0.102 Hom.: 307

Bravo AF: 0.190

Asia WGS AF: 0.264 AC: 919 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

GeneDx

Oct 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.0
Dann	Benign	0.61

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: rs838897; hg19: chr12-125271090; COSMIC: COSV55551195; COSMIC: COSV55551195;