12-124857324-C-T

Position:

• chr12-124857324-C-T

Variant summary

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

The NM_005505.5(SCARB1):​c.126+6271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,182 control chromosomes in the GnomAD database, including 7,709 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 0.29 (7709 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

SCARB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.126+6271G>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.126+6271G>A		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44315 AN: 152066 Hom.: 7706 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.291 AC: 44319 AN: 152182 Hom.: 7709 Cov.: 33 AF XY: 0.291 AC XY: 21670 AN XY: 74420

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.320

Alfa AF: 0.369 Hom.: 9890

Bravo AF: 0.273

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.057
DANN	Benign	0.66

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: rs11615630; hg19: chr12-125341870; COSMIC: COSV55545234;