chr12-21178665-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006446.5(SLCO1B1):c.571T>C(p.Leu191Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,605,080 control chromosomes in the GnomAD database, including 277,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19247 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258238 hom. )

Consequence

SLCO1B1
NM_006446.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.712

Publications

66 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-21178665-T-C is Benign according to our data. Variant chr12-21178665-T-C is described in ClinVar as Benign. ClinVar VariationId is 259984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.712 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 link	c.571T>C	p.Leu191Leu	synonymous_variant	Exon 6 of 15	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3 link	c.571T>C	p.Leu191Leu	synonymous_variant	Exon 6 of 15	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71378

AN:

151912

Hom.:

19248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.484

GnomAD2 exomes

AF:

0.530

AC:

133096

AN:

251042

AF XY:

0.541

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.628

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.588

AC:

854584

AN:

1453050

Hom.:

258238

Cov.:

AF XY:

0.587

AC XY:

424888

AN XY:

723466

show subpopulations

African (AFR)

AF:

0.182

AC:

6044

AN:

33284

American (AMR)

AF:

0.523

AC:

23360

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

16262

AN:

26062

East Asian (EAS)

AF:

0.294

AC:

11633

AN:

39588

South Asian (SAS)

AF:

0.526

AC:

45329

AN:

86132

European-Finnish (FIN)

AF:

0.519

AC:

27735

AN:

53406

Middle Eastern (MID)

AF:

0.547

AC:

3133

AN:

5728

European-Non Finnish (NFE)

AF:

0.623

AC:

687927

AN:

1104040

Other (OTH)

AF:

0.552

AC:

33161

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16735

33470

50206

66941

83676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18118

36236

54354

72472

90590

<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:

0.470

AC:

71384

AN:

152030

Hom.:

19247

Cov.:

AF XY:

0.464

AC XY:

34466

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.204

AC:

8474

AN:

41506

American (AMR)

AF:

0.518

AC:

7911

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2213

AN:

3472

East Asian (EAS)

AF:

0.255

AC:

1321

AN:

5172

South Asian (SAS)

AF:

0.488

AC:

2355

AN:

4824

European-Finnish (FIN)

AF:

0.511

AC:

5396

AN:

10554

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.618

AC:

41991

AN:

67934

Other (OTH)

AF:

0.485

AC:

1020

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1689

3378

5066

6755

8444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.564

Hom.:

78242

Bravo

AF:

0.460

Asia WGS

AF:

0.347

AC:

1203

AN:

3474

EpiCase

AF:

0.617

EpiControl

AF:

0.622

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:4

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLCO1B1-related disorder

Benign:1

Jul 21, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.6

(source)

DANN

Benign

0.25

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over