12-124838694-G-A

Position:

• chr12-124838694-G-A

Variant summary

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

The ENST00000261693.11(SCARB1):​c.127-20987C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,156 control chromosomes in the GnomAD database, including 9,785 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 0.33 (9785 hom., cov: 30)
• Consequence: SCARB1 ENST00000261693.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-20987C>T		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-20987C>T		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50442 AN: 151056 Hom.: 9792 Cov.: 30

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.334 AC: 50430 AN: 151156 Hom.: 9785 Cov.: 30 AF XY: 0.336 AC XY: 24724 AN XY: 73692

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.351

Alfa AF: 0.374 Hom.: 3923

Bravo AF: 0.310

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.76

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: rs12582221; hg19: chr12-125323240;