rs3924313

Variant names:

• chr12-124843829-G-A
• rs3924313
• NM_005505.5:c.126+19766C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005505.5(SCARB1):​c.126+19766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,048 control chromosomes in the GnomAD database, including 5,598 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 0.26 (5598 hom., cov: 31)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.126+19766C>T		intron_variant	Intron 1 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.126+19766C>T		intron_variant	Intron 1 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39906 AN: 151930 Hom.: 5588 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.263 AC: 39948 AN: 152048 Hom.: 5598 Cov.: 31 AF XY: 0.258 AC XY: 19190 AN XY: 74352

African (AFR) AF: 0.203 AC: 8418 AN: 41456

American (AMR) AF: 0.230 AC: 3509 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5176

South Asian (SAS) AF: 0.268 AC: 1295 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2517 AN: 10576

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21515 AN: 67972

Other (OTH) AF: 0.276 AC: 581 AN: 2104

Alfa AF: 0.300 Hom.: 4567

Bravo AF: 0.258

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.44
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3924313; hg19: chr12-125328375;