12-124786227-A-T

Variant names:

• chr12-124786227-A-T
• rs2293440
• NM_005505.5:c.1401+130T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005505.5(SCARB1):​c.1401+130T>A variant causes a intron 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 12 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09063482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1401+130T>A		intron_variant	Intron 11 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1401+130T>A		intron_variant	Intron 11 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.2
DANN	Benign	0.63
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		0.32
PROVEAN	Benign	0.58	N;N
REVEL	Benign	0.029
Sift	Uncertain	0.025	D;D
Sift4G	Benign	0.72	T;T
Polyphen		0.043	B;.
Vest4		0.23
MutPred		0.39		Gain of disorder (P = 0.0018);.;
MVP		0.52
ClinPred		0.059	T
GERP RS		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.062
Mutation Taster		=97/3	polymorphism

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: rs2293440; hg19: chr12-125270773;