rs4238001

Positions:

• chr12-124863717-C-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.4G>A​(p.Gly2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,504,254 control chromosomes in the GnomAD database, including 7,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.086 (665 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7127 hom.)
• Consequence: SCARB1 NM_005505.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.51

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 (MetaRNN=0.002726525).
• BP6: Variant 12-124863717-C-T is Benign according to our data. Variant chr12-124863717-C-T is described in ClinVar as [Benign]. Clinvar id is 1264359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-124863717-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.4G>A	p.Gly2Ser	missense_variant	1/13	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.4G>A	p.Gly2Ser	missense_variant	1/13	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13022 AN: 152116 Hom.: 662 Cov.: 33

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0498

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.102 AC: 11313 AN: 110522 Hom.: 619 AF XY: 0.100 AC XY: 6104 AN XY: 60818

Gnomad AFR exome AF: 0.0780

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.000349

Gnomad SAS exome AF: 0.0692

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.0985 AC: 133227 AN: 1352030 Hom.: 7127 Cov.: 31 AF XY: 0.0987 AC XY: 65779 AN XY: 666466

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.000387

Gnomad4 SAS exome AF: 0.0648

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0857 AC: 13040 AN: 152224 Hom.: 665 Cov.: 33 AF XY: 0.0829 AC XY: 6173 AN XY: 74436

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.108

Alfa AF: 0.104 Hom.: 300

Bravo AF: 0.0876

TwinsUK AF: 0.0995 AC: 369

ALSPAC AF: 0.103 AC: 397

ESP6500AA AF: 0.0525 AC: 221

ESP6500EA AF: 0.0991 AC: 800

ExAC AF: 0.0562 AC: 5335

Asia WGS AF: 0.0470 AC: 161 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 21531995, 27651445, 12519372, 25993026, 19158204, 10397692) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;T;.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.53	T;T;T;T;T
MetaRNN	Benign	0.0027	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	2.0	M;M;M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.78	N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.17	T;T;T;T;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;D;D;.
Vest4		0.062
MPC		1.3
ClinPred		0.029	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.46

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: rs4238001; hg19: chr12-125348263; COSMIC: COSV55547637;