rs1902569

Variant names:

• chr12-124819458-C-T
• rs1902569
• NM_005505.5:c.127-1751G>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.127-1751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,130 control chromosomes in the GnomAD database, including 9,532 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 0.34 (9532 hom., cov: 32)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-1751G>A		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.127-1751G>A		intron_variant	Intron 1 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51477 AN: 152012 Hom.: 9521 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.339 AC: 51511 AN: 152130 Hom.: 9532 Cov.: 32 AF XY: 0.342 AC XY: 25404 AN XY: 74372

African (AFR) AF: 0.195 AC: 8109 AN: 41510

American (AMR) AF: 0.325 AC: 4962 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1129 AN: 5170

South Asian (SAS) AF: 0.466 AC: 2253 AN: 4830

European-Finnish (FIN) AF: 0.415 AC: 4391 AN: 10584

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27731 AN: 67964

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.385 Hom.: 4035

Bravo AF: 0.320

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.28
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: rs1902569; hg19: chr12-125304004;