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GeneBe

12-21172775-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_006446.5(SLCO1B1):c.210C>T(p.Asp70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,612,860 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

SLCO1B1
NM_006446.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.300
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-21172775-C-T is Benign according to our data. Variant chr12-21172775-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1284586.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21172775-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.3 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 31 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B1NM_006446.5 linkuse as main transcriptc.210C>T p.Asp70= synonymous_variant 3/15 ENST00000256958.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B1ENST00000256958.3 linkuse as main transcriptc.210C>T p.Asp70= synonymous_variant 3/151 NM_006446.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152042
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000435
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000945
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000140
AC:
35
AN:
250496
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135470
show subpopulations
Gnomad AFR exome
AF:
0.000493
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000159
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000958
AC:
140
AN:
1460818
Hom.:
0
Cov.:
31
AF XY:
0.0000949
AC XY:
69
AN XY:
726750
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000711
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152042
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.000435
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000945
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000175
Hom.:
0
Bravo
AF:
0.000219
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Rotor syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesDec 30, 2020- -
not provided Benign:1
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
9.6
Dann
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs148697674; hg19: chr12-21325709; COSMIC: COSV57013163; API