12-124778698-G-A

Position:

• chr12-124778698-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005505.5(SCARB1):​c.*1-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 956,776 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (213 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (125 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-124778698-G-A is Benign according to our data. Variant chr12-124778698-G-A is described in ClinVar as [Benign]. Clinvar id is 1254971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.*1-112C>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.*1-112C>T		intron_variant		1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.107 AC: 4172 AN: 39072 Hom.: 213 Cov.: 0

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.0779

GnomAD4 exome AF: 0.00293 AC: 2687 AN: 917652 Hom.: 125 AF XY: 0.00263 AC XY: 1161 AN XY: 441174

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00956

Gnomad4 ASJ exome AF: 0.000513

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000835

Gnomad4 FIN exome AF: 0.0000337

Gnomad4 NFE exome AF: 0.000283

Gnomad4 OTH exome AF: 0.00783

GnomAD4 genome AF: 0.107 AC: 4177 AN: 39124 Hom.: 213 Cov.: 0 AF XY: 0.104 AC XY: 1954 AN XY: 18802

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00273

Gnomad4 OTH AF: 0.0763

Alfa AF: 0.0177 Hom.: 14

Bravo AF: 0.0335

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 27, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs747155; hg19: chr12-125263244;