Menu
GeneBe

rs4149056

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_006446.5(SLCO1B1):c.521T>A(p.Val174Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V174A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SLCO1B1
NM_006446.5 missense

Scores

7
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.58
Variant links:
Genes affected
SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr12-21178615-T-C is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B1NM_006446.5 linkuse as main transcriptc.521T>A p.Val174Glu missense_variant 6/15 ENST00000256958.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B1ENST00000256958.3 linkuse as main transcriptc.521T>A p.Val174Glu missense_variant 6/151 NM_006446.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.040
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.42
Eigen_PC
Benign
0.19
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0078
T
MetaRNN
Pathogenic
0.90
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Pathogenic
3.7
H
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-5.8
D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.63
Loss of helix (P = 0.1299);
MVP
0.48
MPC
0.066
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.89
gMVP
0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21331549; API