12-124800202-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005505.5(SCARB1):​c.1050T>G​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A350A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.31
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-6.31 with no splicing effect.

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>G	p.Ala350Ala	synonymous	Exon 8 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.1050T>G	p.Ala350Ala	synonymous	Exon 8 of 12	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.927T>G	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>G	p.Ala350Ala	synonymous	Exon 8 of 13	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.1050T>G	p.Ala350Ala	synonymous	Exon 8 of 13	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.1365T>G		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.016
DANN	Benign	0.38
PhyloP100		-6.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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;