chr12-124777047-C-T

Position:

• chr12-124777047-C-T

Variant summary

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

The NM_005505.5(SCARB1):​c.*1540G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,888 control chromosomes in the GnomAD database, including 25,173 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 0.55 (25173 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCARB1 NM_005505.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.*1540G>A		3_prime_UTR_variant	13/13	ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.*1540G>A		3_prime_UTR_variant	13/13	1	NM_005505.5	P3
SCARB1	ENST00000339570.9	c.*1420G>A		3_prime_UTR_variant	12/12	5		A1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84270 AN: 151770 Hom.: 25174 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.600

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.555 AC: 84283 AN: 151888 Hom.: 25173 Cov.: 31 AF XY: 0.551 AC XY: 40857 AN XY: 74216

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.595

Alfa AF: 0.656 Hom.: 43394

Bravo AF: 0.548

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs838880; hg19: chr12-125261593;