chr12-124790868-T-G

Position:

• chr12-124790868-T-G

Variant summary

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

The NM_005505.5(SCARB1):​c.1203-3411A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,318 control chromosomes in the GnomAD database, including 1,482 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 0.099 (1482 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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]

LOC124903046 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1203-3411A>C		intron_variant		ENST00000261693.11	NP_005496.4
LOC124903046	XR_007063510.1	n.2492T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1203-3411A>C		intron_variant		1	NM_005505.5	ENSP00000261693	P3
	ENST00000657226.1	n.1125+1347T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15092 AN: 152200 Hom.: 1467 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0995 AC: 15153 AN: 152318 Hom.: 1482 Cov.: 33 AF XY: 0.103 AC XY: 7653 AN XY: 74486

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0527 Hom.: 75

Bravo AF: 0.116

Asia WGS AF: 0.238 AC: 827 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	2.0
DANN	Benign	0.24

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: rs838864; hg19: chr12-125275414;