12-124848409-T-C

Position:

• chr12-124848409-T-C

Variant summary

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

The NM_005505.5(SCARB1):​c.126+15186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,136 control chromosomes in the GnomAD database, including 32,035 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 (32035 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.126+15186A>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.126+15186A>G		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97955 AN: 152016 Hom.: 31973 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.645 AC: 98081 AN: 152136 Hom.: 32035 Cov.: 33 AF XY: 0.647 AC XY: 48126 AN XY: 74382

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.658

Alfa AF: 0.600 Hom.: 42460

Bravo AF: 0.654

Asia WGS AF: 0.702 AC: 2439 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	0.94
DANN	Benign	0.33

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: rs10773111; hg19: chr12-125332955;