12-124836304-C-T

Position:

• chr12-124836304-C-T

Variant summary

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

The ENST00000261693.11(SCARB1):​c.127-18597G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,038 control chromosomes in the GnomAD database, including 11,469 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 0.38 (11469 hom., cov: 32)
• Consequence: SCARB1 ENST00000261693.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-18597G>A		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-18597G>A		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58087 AN: 151920 Hom.: 11448 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 58144 AN: 152038 Hom.: 11469 Cov.: 32 AF XY: 0.384 AC XY: 28569 AN XY: 74308

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.413

Alfa AF: 0.354 Hom.: 16121

Bravo AF: 0.400

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.52
DANN	Benign	0.71

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: rs4765623; hg19: chr12-125320850;