12-124815284-C-T

Position:

• chr12-124815284-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005505.5(SCARB1):​c.285-170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,050 control chromosomes in the GnomAD database, including 18,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18099 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.75

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-124815284-C-T is Benign according to our data. Variant chr12-124815284-C-T is described in ClinVar as [Benign]. Clinvar id is 1181708.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-124815284-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.285-170G>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.285-170G>A		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73847 AN: 151932 Hom.: 18087 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.486 AC: 73898 AN: 152050 Hom.: 18099 Cov.: 33 AF XY: 0.481 AC XY: 35777 AN XY: 74304

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.484

Alfa AF: 0.505 Hom.: 18301

Bravo AF: 0.486

Asia WGS AF: 0.393 AC: 1372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0090
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4765615; hg19: chr12-125299830;