12-124815926-G-T

Variant names:

• chr12-124815926-G-T
• rs745529
• NM_005505.5:c.285-812C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.86).
• 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 rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.285-812C>A		intron_variant	Intron 2 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.285-812C>A		intron_variant	Intron 2 of 12	1	NM_005505.5	ENSP00000261693.6

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

African (AFR) AF: 0.199 AC: 8267 AN: 41442

American (AMR) AF: 0.243 AC: 3711 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3462

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5168

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4814

European-Finnish (FIN) AF: 0.240 AC: 2523 AN: 10514

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21041 AN: 67944

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.299 Hom.: 30598

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
PhyloP100		1.1
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: rs745529; hg19: chr12-125300472;