12-124785146-G-C

Position:

• chr12-124785146-G-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+1211C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,338 control chromosomes in the GnomAD database, including 31,126 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 0.63 (31065 hom., cov: 33)
  • Exomes 𝑓: 0.71 (61 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1401+1211C>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+1211C>G		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96432 AN: 151974 Hom.: 31058 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.623

GnomAD4 exome AF: 0.711 AC: 175 AN: 246 Hom.: 61 Cov.: 0 AF XY: 0.710 AC XY: 125 AN XY: 176

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.634 AC: 96465 AN: 152092 Hom.: 31065 Cov.: 33 AF XY: 0.631 AC XY: 46932 AN XY: 74348

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.621

Alfa AF: 0.537 Hom.: 1474

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
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: rs838895; hg19: chr12-125269692;