rs5888

Variant names:

• chr12-124800202-A-G
• rs5888
• NM_005505.5:c.1050T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-124800202-A-G
• chr12-124800202-A-C
• chr12-124800202-A-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.1050T>C​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,832 control chromosomes in the GnomAD database, including 248,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31231 hom., cov: 32)
  • Exomes 𝑓: 0.54 (217210 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.31
• Publications: 117 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]

ENSG00000287242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-124800202-A-G is Benign according to our data. Variant chr12-124800202-A-G is described in ClinVar as Benign. ClinVar VariationId is 1236346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 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.1050T>C	p.Ala350Ala	synonymous	Exon 8 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.1050T>C	p.Ala350Ala	synonymous	Exon 8 of 12	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.927T>C	p.Ala309Ala	synonymous	Exon 8 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.1050T>C	p.Ala350Ala	synonymous	Exon 8 of 13	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.1050T>C	p.Ala350Ala	synonymous	Exon 8 of 13	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.1365T>C		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95273 AN: 151928 Hom.: 31181 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.605

GnomAD2 exomes AF: 0.588 AC: 147686 AN: 251150 AF XY: 0.576

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.541 AC: 789584 AN: 1460786 Hom.: 217210 Cov.: 42 AF XY: 0.538 AC XY: 391323 AN XY: 726740

African (AFR) AF: 0.822 AC: 27501 AN: 33464

American (AMR) AF: 0.681 AC: 30472 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 11139 AN: 26122

East Asian (EAS) AF: 0.765 AC: 30363 AN: 39690

South Asian (SAS) AF: 0.533 AC: 45984 AN: 86238

European-Finnish (FIN) AF: 0.592 AC: 31571 AN: 53342

Middle Eastern (MID) AF: 0.534 AC: 3072 AN: 5756

European-Non Finnish (NFE) AF: 0.519 AC: 576124 AN: 1111104

Other (OTH) AF: 0.553 AC: 33358 AN: 60356

GnomAD4 genome AF: 0.627 AC: 95381 AN: 152046 Hom.: 31231 Cov.: 32 AF XY: 0.630 AC XY: 46829 AN XY: 74336

African (AFR) AF: 0.812 AC: 33681 AN: 41502

American (AMR) AF: 0.641 AC: 9788 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3470

East Asian (EAS) AF: 0.749 AC: 3870 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2625 AN: 4820

European-Finnish (FIN) AF: 0.608 AC: 6441 AN: 10586

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35553 AN: 67914

Other (OTH) AF: 0.603 AC: 1273 AN: 2110

Alfa AF: 0.551 Hom.: 67133

Bravo AF: 0.640

Asia WGS AF: 0.638 AC: 2218 AN: 3478

EpiCase AF: 0.519

EpiControl AF: 0.518

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	-0.98
CADD	Benign	0.018
DANN	Benign	0.38
PhyloP100		-6.3
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

Other links and lift over

dbSNP: rs5888; hg19: chr12-125284748; COSMIC: COSV55550544;