chr12-124804719-G-A

Position:

• chr12-124804719-G-A

Variant summary

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

The NM_005505.5(SCARB1):​c.1009+3042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,086 control chromosomes in the GnomAD database, including 13,139 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 0.40 (13139 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1009+3042C>T		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1009+3042C>T		intron_variant		1	NM_005505.5	ENSP00000261693	P3
	ENST00000657226.1	n.1126-2891G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61436 AN: 151966 Hom.: 13136 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.404 AC: 61453 AN: 152086 Hom.: 13139 Cov.: 33 AF XY: 0.407 AC XY: 30226 AN XY: 74348

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.420

Alfa AF: 0.453 Hom.: 33216

Bravo AF: 0.383

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3782287; hg19: chr12-125289265;