rs2293440

Positions:

• chr12-124786227-A-G
• chr12-124786227-A-T

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.1401+130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,598,270 control chromosomes in the GnomAD database, including 13,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3690 hom., cov: 33)
  • Exomes 𝑓: 0.063 (9376 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.324

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 (MetaRNN=4.0113926E-4).
• BP6: Variant 12-124786227-A-G is Benign according to our data. Variant chr12-124786227-A-G is described in ClinVar as [Benign]. Clinvar id is 1246761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124786227-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1401+130T>C		intron_variant		ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1401+130T>C		intron_variant		1	NM_005505.5	ENSP00000261693	P3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23974 AN: 152082 Hom.: 3666 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.141

GnomAD3 exomes AF: 0.128 AC: 29672 AN: 231230 Hom.: 4221 AF XY: 0.112 AC XY: 14320 AN XY: 127354

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.0746

Gnomad EAS exome AF: 0.431

Gnomad SAS exome AF: 0.0745

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0350

Gnomad OTH exome AF: 0.0932

GnomAD4 exome AF: 0.0633 AC: 91551 AN: 1446070 Hom.: 9376 Cov.: 32 AF XY: 0.0620 AC XY: 44614 AN XY: 719732

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0942

GnomAD4 genome AF: 0.158 AC: 24058 AN: 152200 Hom.: 3690 Cov.: 33 AF XY: 0.159 AC XY: 11836 AN XY: 74428

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0624 Hom.: 646

Bravo AF: 0.183

TwinsUK AF: 0.0345 AC: 128

ALSPAC AF: 0.0265 AC: 102

ExAC AF: 0.116 AC: 14024

Asia WGS AF: 0.250 AC: 868 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.6
DANN	Benign	0.65
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.00040	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.045
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.0	B;.
Vest4		0.077
ClinPred		0.0020	T
GERP RS		0.13
Varity_R		0.19

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: rs2293440; hg19: chr12-125270773; COSMIC: COSV55543760;