12-124786572-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.1255-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,592,236 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (106 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (84 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-124786572-C-T is Benign according to our data. Variant chr12-124786572-C-T is described in ClinVar as [Benign]. Clinvar id is 1275395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARB1	NM_005505.5	c.1255-69G>A		intron_variant		ENST00000261693.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB1	ENST00000261693.11	c.1255-69G>A		intron_variant		1	NM_005505.5	P3

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3144 AN: 152234 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00218 AC: 3142 AN: 1439884 Hom.: 84 AF XY: 0.00186 AC XY: 1330 AN XY: 715550

Gnomad4 AFR exome AF: 0.0680

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000271

Gnomad4 FIN exome AF: 0.0000656

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.0207 AC: 3158 AN: 152352 Hom.: 106 Cov.: 33 AF XY: 0.0194 AC XY: 1447 AN XY: 74496

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.00751

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0125 Hom.: 11

Bravo AF: 0.0235

Asia WGS AF: 0.00404 AC: 14 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

Apr 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.6
Dann	Benign	0.64

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: rs838898; hg19: chr12-125271118;