12-21202555-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006446.5(SLCO1B1):c.1200C>G(p.Phe400Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,611,774 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 45 hom. )

Consequence

SLCO1B1
NM_006446.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.02

Publications

13 publications found

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]

SLCO1B1 Gene-Disease associations (from GenCC):

Rotor syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLCO1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035394728).

BP6

Variant 12-21202555-C-G is Benign according to our data. Variant chr12-21202555-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 307946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0139 (2114/151882) while in subpopulation AFR AF = 0.0484 (2005/41430). AF 95% confidence interval is 0.0466. There are 47 homozygotes in GnomAd4. There are 996 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006446.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.1200C>G	p.Phe400Leu	missense	Exon 10 of 15	NP_006437.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.1200C>G	p.Phe400Leu	missense	Exon 10 of 15	ENSP00000256958.2

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2114

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00506

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.00347

AC:

867

AN:

250146

AF XY:

0.00252

show subpopulations

Gnomad AFR exome

AF:

0.0486

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00140

AC:

2039

AN:

1459892

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

869

AN XY:

726282

show subpopulations

African (AFR)

AF:

0.0505

AC:

1683

AN:

33344

American (AMR)

AF:

0.00202

AC:

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53254

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000963

AC:

107

AN:

1111024

Other (OTH)

AF:

0.00254

AC:

153

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

175

263

350

438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0139

AC:

2114

AN:

151882

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

996

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.0484

AC:

2005

AN:

41430

American (AMR)

AF:

0.00506

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67930

Other (OTH)

AF:

0.00996

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

103

206

309

412

515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.0159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00429

AC:

521

Asia WGS

AF:

0.00404

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Rotor syndrome (2)

SLCO1B1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.4

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.18

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.24

PhyloP100

-1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.078

Sift

Benign

0.13

Sift4G

Uncertain

0.035

Polyphen

0.18

Vest4

0.11

MutPred

0.82

Loss of methylation at K401 (P = 0.0343)

MVP

0.16

MPC

0.011

ClinPred

0.026

GERP RS

-0.29

Varity_R

0.19

gMVP

0.29

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over