12-124811816-G-A

Position:

• chr12-124811816-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.726+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 1,298,030 control chromosomes in the GnomAD database, including 5,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (440 hom., cov: 32)
  • Exomes 𝑓: 0.085 (4732 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.80

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 12-124811816-G-A is Benign according to our data. Variant chr12-124811816-G-A is described in ClinVar as [Benign]. Clinvar id is 1250072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.726+54C>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.726+54C>T		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9396 AN: 151948 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0287

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0849 AC: 97260 AN: 1145964 Hom.: 4732 AF XY: 0.0834 AC XY: 48374 AN XY: 580350

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.0697

Gnomad4 EAS exome AF: 0.000141

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0768

GnomAD4 genome AF: 0.0618 AC: 9391 AN: 152066 Hom.: 440 Cov.: 32 AF XY: 0.0577 AC XY: 4290 AN XY: 74328

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0285

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0973

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0322 Hom.: 28

Bravo AF: 0.0622

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 10, 2019	This variant is associated with the following publications: (PMID: 10397692) -
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	-1.1
CADD	Benign	0.26
DANN	Benign	0.90
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: rs61932577; hg19: chr12-125296362;