12-124784777-A-C

Position:

• chr12-124784777-A-C

Variant summary

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

The NM_005505.5(SCARB1):​c.1401+1580T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,320 control chromosomes in the GnomAD database, including 31,749 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 0.64 (31706 hom., cov: 33)
  • Exomes 𝑓: 0.66 (43 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1401+1580T>G		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1401+1580T>G		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97334 AN: 152000 Hom.: 31698 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.663 AC: 134 AN: 202 Hom.: 43 Cov.: 0 AF XY: 0.667 AC XY: 100 AN XY: 150

Gnomad4 AFR exome AF: 0.833

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.640 AC: 97370 AN: 152118 Hom.: 31706 Cov.: 33 AF XY: 0.638 AC XY: 47410 AN XY: 74360

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.626

Alfa AF: 0.678 Hom.: 71574

Bravo AF: 0.628

Asia WGS AF: 0.572 AC: 1990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.4
DANN	Benign	0.49

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: rs838892; hg19: chr12-125269323;