chr12-20862972-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019844.4(SLCO1B3):​c.727+118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 515,374 control chromosomes in the GnomAD database, including 4,654 homozygotes. 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: 𝑓 0.10 ( 1126 hom., cov: 32)
Exomes 𝑓: 0.13 ( 3528 hom. )

Consequence

SLCO1B3
NM_019844.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10
Variant links:
Genes affected
SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) 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 endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLCO1B3NM_019844.4 linkuse as main transcriptc.727+118C>G intron_variant ENST00000381545.8 NP_062818.1 Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7NM_001371097.1 linkuse as main transcriptc.727+118C>G intron_variant NP_001358026.1
SLCO1B3NM_001349920.2 linkuse as main transcriptc.643+118C>G intron_variant NP_001336849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLCO1B3ENST00000381545.8 linkuse as main transcriptc.727+118C>G intron_variant 2 NM_019844.4 ENSP00000370956.4 Q9NPD5-1
SLCO1B3-SLCO1B7ENST00000540229.1 linkuse as main transcriptc.727+118C>G intron_variant 2 ENSP00000441269.1 A0A0A6YYJ9

Frequencies

GnomAD3 genomes
AF:
0.105
AC:
15917
AN:
152012
Hom.:
1128
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0291
Gnomad AMI
AF:
0.188
Gnomad AMR
AF:
0.109
Gnomad ASJ
AF:
0.193
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.0679
Gnomad FIN
AF:
0.102
Gnomad MID
AF:
0.223
Gnomad NFE
AF:
0.153
Gnomad OTH
AF:
0.138
GnomAD4 exome
AF:
0.127
AC:
46083
AN:
363246
Hom.:
3528
AF XY:
0.128
AC XY:
24214
AN XY:
189904
show subpopulations
Gnomad4 AFR exome
AF:
0.0282
Gnomad4 AMR exome
AF:
0.0829
Gnomad4 ASJ exome
AF:
0.195
Gnomad4 EAS exome
AF:
0.000230
Gnomad4 SAS exome
AF:
0.0653
Gnomad4 FIN exome
AF:
0.101
Gnomad4 NFE exome
AF:
0.152
Gnomad4 OTH exome
AF:
0.133
GnomAD4 genome
AF:
0.105
AC:
15912
AN:
152128
Hom.:
1126
Cov.:
32
AF XY:
0.100
AC XY:
7448
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0291
Gnomad4 AMR
AF:
0.109
Gnomad4 ASJ
AF:
0.193
Gnomad4 EAS
AF:
0.00174
Gnomad4 SAS
AF:
0.0682
Gnomad4 FIN
AF:
0.102
Gnomad4 NFE
AF:
0.153
Gnomad4 OTH
AF:
0.136
Alfa
AF:
0.120
Hom.:
158
Bravo
AF:
0.104
Asia WGS
AF:
0.0330
AC:
114
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.28
DANN
Benign
0.70

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

LitVar

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

Other links and lift over

dbSNP: rs17680137; hg19: chr12-21015906; COSMIC: COSV53945888; COSMIC: COSV53945888; API