rs7954519

chr12-124835609-T-G

Variant summary

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

The NM_005505.5(SCARB1):c.127-17902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,724 control chromosomes in the GnomAD database, including 3,034 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 0.20 (3034 hom., cov: 31)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.127-17902A>C		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-17902A>C		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29793 AN: 151604 Hom.: 3026 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.197 AC: 29833 AN: 151724 Hom.: 3034 Cov.: 31 AF XY: 0.195 AC XY: 14482 AN XY: 74130

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.183

Alfa AF: 0.192 Hom.: 725

Bravo AF: 0.195

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.8
Dann	Benign	0.75

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: rs7954519; hg19: chr12-125320155;