rs838891

Positions:

• chr12-124783886-G-A

Variant summary

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

The NM_005505.5(SCARB1):​c.1402-1075C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,140 control chromosomes in the GnomAD database, including 30,032 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 0.62 (30031 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

SCARB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1402-1075C>T		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1402-1075C>T		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94595 AN: 152014 Hom.: 30023 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.622 AC: 94631 AN: 152132 Hom.: 30031 Cov.: 33 AF XY: 0.620 AC XY: 46136 AN XY: 74380

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.614

Alfa AF: 0.644 Hom.: 8795

Bravo AF: 0.609

Asia WGS AF: 0.551 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.065
DANN	Benign	0.65

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: rs838891; hg19: chr12-125268432;