12-124834226-C-T

Position:

• chr12-124834226-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.127-16519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,154 control chromosomes in the GnomAD database, including 18,853 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 0.49 (18853 hom., cov: 34)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.127-16519G>A		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.127-16519G>A		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74384 AN: 152036 Hom.: 18833 Cov.: 34

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.489 AC: 74455 AN: 152154 Hom.: 18853 Cov.: 34 AF XY: 0.486 AC XY: 36184 AN XY: 74378

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.489

Alfa AF: 0.452 Hom.: 27519

Bravo AF: 0.491

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0030
DANN	Benign	0.32

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: rs4765180; hg19: chr12-125318772;