12-124782744-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005505.5(SCARB1):​c.1469A>T​(p.Tyr490Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCARB1
NM_005505.5 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.18325123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCARB1NM_005505.5 linkc.1469A>T p.Tyr490Phe missense_variant Exon 12 of 13 ENST00000261693.11 NP_005496.4 Q8WTV0-2A0A024RBS4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCARB1ENST00000261693.11 linkc.1469A>T p.Tyr490Phe missense_variant Exon 12 of 13 1 NM_005505.5 ENSP00000261693.6 Q8WTV0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251436
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460680
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726716
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33460
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110894
Other (OTH)
AF:
0.00
AC:
0
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1469A>T (p.Y490F) alteration is located in exon 12 (coding exon 12) of the SCARB1 gene. This alteration results from a A to T substitution at nucleotide position 1469, causing the tyrosine (Y) at amino acid position 490 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.015
.;T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.73
T
PhyloP100
1.3
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.20
Sift
Benign
0.61
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.93
P;P
Vest4
0.28
MutPred
0.33
.;Loss of phosphorylation at Y462 (P = 0.017);
MVP
0.35
MPC
0.42
ClinPred
0.92
D
GERP RS
5.4
gMVP
0.057
Mutation Taster
=90/10
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

Publications

Other links and lift over

dbSNP: rs747280593; hg19: chr12-125267290; API