12-20815710-AATATTCACTTGGTATCTG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_019844.4(SLCO1B3):​c.-28_-11delATATTCACTTGGTATCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,469,848 control chromosomes in the GnomAD database, including 54,843 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4628 hom., cov: 23)
Exomes 𝑓: 0.27 ( 50215 hom. )

Consequence

SLCO1B3
NM_019844.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.607
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 -16 ACMG points.

BP6
Variant 12-20815710-AATATTCACTTGGTATCTG-A is Benign according to our data. Variant chr12-20815710-AATATTCACTTGGTATCTG-A is described in ClinVar as [Benign]. Clinvar id is 993345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLCO1B3NM_019844.4 linkuse as main transcriptc.-28_-11delATATTCACTTGGTATCTG 5_prime_UTR_variant 3/16 ENST00000381545.8 NP_062818.1 Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7NM_001371097.1 linkuse as main transcriptc.-28_-11delATATTCACTTGGTATCTG 5_prime_UTR_variant 1/16 NP_001358026.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLCO1B3ENST00000381545.8 linkuse as main transcriptc.-28_-11delATATTCACTTGGTATCTG 5_prime_UTR_variant 3/162 NM_019844.4 ENSP00000370956.4 Q9NPD5-1
SLCO1B3-SLCO1B7ENST00000540229.1 linkuse as main transcriptc.-28_-11delATATTCACTTGGTATCTG 5_prime_UTR_variant 1/162 ENSP00000441269.1 A0A0A6YYJ9

Frequencies

GnomAD3 genomes
AF:
0.234
AC:
35565
AN:
152042
Hom.:
4629
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.135
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.221
Gnomad ASJ
AF:
0.263
Gnomad EAS
AF:
0.169
Gnomad SAS
AF:
0.161
Gnomad FIN
AF:
0.255
Gnomad MID
AF:
0.347
Gnomad NFE
AF:
0.300
Gnomad OTH
AF:
0.261
GnomAD3 exomes
AF:
0.140
AC:
29724
AN:
212094
Hom.:
3670
AF XY:
0.149
AC XY:
17141
AN XY:
115188
show subpopulations
Gnomad AFR exome
AF:
0.0751
Gnomad AMR exome
AF:
0.0686
Gnomad ASJ exome
AF:
0.135
Gnomad EAS exome
AF:
0.0765
Gnomad SAS exome
AF:
0.0867
Gnomad FIN exome
AF:
0.144
Gnomad NFE exome
AF:
0.197
Gnomad OTH exome
AF:
0.134
GnomAD4 exome
AF:
0.272
AC:
358538
AN:
1317686
Hom.:
50215
AF XY:
0.269
AC XY:
177123
AN XY:
659148
show subpopulations
Gnomad4 AFR exome
AF:
0.124
Gnomad4 AMR exome
AF:
0.147
Gnomad4 ASJ exome
AF:
0.242
Gnomad4 EAS exome
AF:
0.156
Gnomad4 SAS exome
AF:
0.133
Gnomad4 FIN exome
AF:
0.239
Gnomad4 NFE exome
AF:
0.299
Gnomad4 OTH exome
AF:
0.265
GnomAD4 genome
AF:
0.234
AC:
35591
AN:
152162
Hom.:
4628
Cov.:
23
AF XY:
0.230
AC XY:
17135
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.135
Gnomad4 AMR
AF:
0.221
Gnomad4 ASJ
AF:
0.263
Gnomad4 EAS
AF:
0.169
Gnomad4 SAS
AF:
0.161
Gnomad4 FIN
AF:
0.255
Gnomad4 NFE
AF:
0.300
Gnomad4 OTH
AF:
0.262
Alfa
AF:
0.223
Hom.:
843
Asia WGS
AF:
0.161
AC:
557
AN:
3470

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Rotor syndrome Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 30, 2023- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs527574443; hg19: chr12-20968644; COSMIC: COSV53933007; API