12-124815926-G-T

Variant summary

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

The NM_005505.5(SCARB1):c.285-812C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,946 control chromosomes in the GnomAD database, including 5,993 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 0.27 (5993 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.285-812C>A		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.285-812C>A		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41483 AN: 151830 Hom.: 5982 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.273 AC: 41521 AN: 151946 Hom.: 5993 Cov.: 32 AF XY: 0.274 AC XY: 20370 AN XY: 74250

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.303

Alfa AF: 0.307 Hom.: 15074

Bravo AF: 0.265

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.8
Dann	Benign	0.92

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: rs745529; hg19: chr12-125300472;