chr12-21021574-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371097.1(SLCO1B3-SLCO1B7):​c.1866-45745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,521,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SLCO1B3-SLCO1B7
NM_001371097.1 intron

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.603
Variant links:
Genes affected
SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]
SLCO1B7 (HGNC:32934): (solute carrier organic anion transporter family member 1B7 (putative)) Predicted to enable bile acid transmembrane transporter activity and sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in bile acid and bile salt transport and sodium-independent organic anion transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.072292835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LOC124902894XM_047429949.1 linkc.332T>C p.Ile111Thr missense_variant Exon 4 of 10 XP_047285905.1
SLCO1B3-SLCO1B7NM_001371097.1 linkc.1866-45745T>C intron_variant Intron 13 of 15 NP_001358026.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO1B3-SLCO1B7ENST00000540229.1 linkc.1866-45745T>C intron_variant Intron 13 of 15 2 ENSP00000441269.1 A0A0A6YYJ9
SLCO1B3-SLCO1B7ENST00000381541.7 linkc.473T>C p.Ile158Thr missense_variant Exon 4 of 14 2 ENSP00000370952.3 F5H094-1
SLCO1B7ENST00000648739.1 linkn.473T>C non_coding_transcript_exon_variant Exon 4 of 14

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151942
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000292
AC:
4
AN:
1369866
Hom.:
0
Cov.:
26
AF XY:
0.00000293
AC XY:
2
AN XY:
681834
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000130
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000190
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151942
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74192
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.332T>C (p.I111T) alteration is located in exon 3 (coding exon 3) of the SLCO1B7 gene. This alteration results from a T to C substitution at nucleotide position 332, causing the isoleucine (I) at amino acid position 111 to be replaced by a threonine (T). 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
AlphaMissense
Benign
0.050
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
1.2
DANN
Benign
0.87
DEOGEN2
Benign
0.0053
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.082
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;N
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.083
Sift
Benign
0.057
T;T
Sift4G
Benign
0.61
T;T
Polyphen
0.0030
.;B
Vest4
0.018
MutPred
0.44
Gain of catalytic residue at R160 (P = 0.0103);.;
MVP
0.061
MPC
0.0057
ClinPred
0.22
T
GERP RS
2.8
Varity_R
0.11
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1469410899; hg19: chr12-21174508; API