rs4238001

Variant names:

• chr12-124863717-C-T
• rs4238001
• NM_005505.5:c.4G>A
• SCARB1 p.Gly2Ser

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 58 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1264359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.4G>A	p.Gly2Ser	missense	Exon 1 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.4G>A	p.Gly2Ser	missense	Exon 1 of 12	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367983.1		c.4G>A	p.Gly2Ser	missense	Exon 1 of 13	NP_001354912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.4G>A	p.Gly2Ser	missense	Exon 1 of 13	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.4G>A	p.Gly2Ser	missense	Exon 1 of 13	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.441+3272G>A		intron	N/A

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

GnomAD2 exomes AF: 0.102 AC: 11313 AN: 110522 AF XY: 0.100

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 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

African (AFR) AF: 0.0578 AC: 1572 AN: 27212

American (AMR) AF: 0.115 AC: 3431 AN: 29826

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3793 AN: 23368

East Asian (EAS) AF: 0.000387 AC: 12 AN: 30978

South Asian (SAS) AF: 0.0648 AC: 4831 AN: 74536

European-Finnish (FIN) AF: 0.0703 AC: 3351 AN: 47656

Middle Eastern (MID) AF: 0.147 AC: 814 AN: 5530

European-Non Finnish (NFE) AF: 0.104 AC: 109837 AN: 1057248

Other (OTH) AF: 0.100 AC: 5586 AN: 55676

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

African (AFR) AF: 0.0540 AC: 2246 AN: 41558

American (AMR) AF: 0.113 AC: 1730 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5170

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4834

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10614

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7130 AN: 67966

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.0994 Hom.: 447

Bravo AF: 0.0876

Asia WGS AF: 0.0470 AC: 161 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.18
Sift	Benign	0.17	T
Sift4G	Pathogenic	0.0	D
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.46
Mutation Taster		=98/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4238001;

hg19: chr12-125348263;

COSMIC: COSV55547637;