chr12-124814331-G-A

Variant names:

• chr12-124814331-G-A
• rs5889
• NM_005505.5:c.501C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005505.5(SCARB1):​c.501C>T​(p.Gly167Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,134 control chromosomes in the GnomAD database, including 5,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (557 hom., cov: 32)
  • Exomes 𝑓: 0.023 (5279 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.60
• Publications: 20 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-124814331-G-A is Benign according to our data. Variant chr12-124814331-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 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.501C>T	p.Gly167Gly	synonymous	Exon 4 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.501C>T	p.Gly167Gly	synonymous	Exon 4 of 12	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.378C>T	p.Gly126Gly	synonymous	Exon 4 of 11	NP_001354911.1	B3KW46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.501C>T	p.Gly167Gly	synonymous	Exon 4 of 13	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.501C>T	p.Gly167Gly	synonymous	Exon 4 of 13	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.816C>T		non_coding_transcript_exon	Exon 5 of 13

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4467 AN: 152172 Hom.: 556 Cov.: 32

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.0315

GnomAD2 exomes AF: 0.0637 AC: 16024 AN: 251470 AF XY: 0.0558

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.403

Gnomad FIN exome AF: 0.00868

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.0389

GnomAD4 exome AF: 0.0225 AC: 32921 AN: 1461844 Hom.: 5279 Cov.: 32 AF XY: 0.0223 AC XY: 16204 AN XY: 727220

African (AFR) AF: 0.00251 AC: 84 AN: 33478

American (AMR) AF: 0.179 AC: 7984 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26136

East Asian (EAS) AF: 0.456 AC: 18120 AN: 39700

South Asian (SAS) AF: 0.0388 AC: 3344 AN: 86246

European-Finnish (FIN) AF: 0.00812 AC: 434 AN: 53420

Middle Eastern (MID) AF: 0.00383 AC: 22 AN: 5744

European-Non Finnish (NFE) AF: 0.00101 AC: 1127 AN: 1112004

Other (OTH) AF: 0.0287 AC: 1735 AN: 60392

GnomAD4 genome AF: 0.0293 AC: 4469 AN: 152290 Hom.: 557 Cov.: 32 AF XY: 0.0342 AC XY: 2543 AN XY: 74462

African (AFR) AF: 0.00366 AC: 152 AN: 41566

American (AMR) AF: 0.109 AC: 1662 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2063 AN: 5174

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4822

European-Finnish (FIN) AF: 0.00904 AC: 96 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68018

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0145 Hom.: 769

Bravo AF: 0.0387

Asia WGS AF: 0.163 AC: 565 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	SCARB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.47
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs5889; hg19: chr12-125298877; COSMIC: COSV55547864; COSMIC: COSV55547864;