NM_006446.5:c.411G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006446.5(SLCO1B1):c.411G>A(p.Ser137Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,505,436 control chromosomes in the GnomAD database, including 11,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1195 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10719 hom. )

Consequence

SLCO1B1
NM_006446.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.153

Publications

38 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:

ENSG00000257062 (HGNC:):

ENSG00000257062 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 (BayesDel_noAF=-0.9).

BP6

Variant 12-21176827-G-A is Benign according to our data. Variant chr12-21176827-G-A is described in ClinVar as Benign. ClinVar VariationId is 307936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 link	c.411G>A	p.Ser137Ser	synonymous_variant	Exon 5 of 15	ENST00000256958.3	NP_006437.3	Q9Y6L6Q05CV5A0A024RAU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLCO1B1	ENST00000256958.3 link	c.411G>A	p.Ser137Ser	synonymous_variant	Exon 5 of 15	1	NM_006446.5	ENSP00000256958.2	Q9Y6L6
ENSG00000257062	ENST00000543498.5 link	n.*193G>A		non_coding_transcript_exon_variant	Exon 6 of 6	4		ENSP00000454306.1	H3BMA8
ENSG00000257062	ENST00000543498.5 link	n.*193G>A		3_prime_UTR_variant	Exon 6 of 6	4		ENSP00000454306.1	H3BMA8

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16488

AN:

151934

Hom.:

1196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0413

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.106

GnomAD2 exomes

AF:

0.111

AC:

27884

AN:

250236

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.0355

Gnomad AMR exome

AF:

0.0683

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.114

AC:

153953

AN:

1353384

Hom.:

10719

Cov.:

AF XY:

0.112

AC XY:

75928

AN XY:

676984

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0263

AC:

840

AN:

31906

American (AMR)

AF:

0.0648

AC:

2860

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4385

AN:

24624

East Asian (EAS)

AF:

0.000255

AC:

AN:

39268

South Asian (SAS)

AF:

0.0414

AC:

3520

AN:

85002

European-Finnish (FIN)

AF:

0.0928

AC:

4771

AN:

51432

Middle Eastern (MID)

AF:

0.0894

AC:

490

AN:

5484

European-Non Finnish (NFE)

AF:

0.129

AC:

131107

AN:

1015038

Other (OTH)

AF:

0.106

AC:

5970

AN:

56512

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.379

Heterozygous variant carriers

5234

10468

15702

20936

26170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4346

8692

13038

17384

21730

<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:

0.108

AC:

16480

AN:

152052

Hom.:

1195

Cov.:

AF XY:

0.104

AC XY:

7697

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0374

AC:

1554

AN:

41530

American (AMR)

AF:

0.0961

AC:

1467

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

736

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4814

European-Finnish (FIN)

AF:

0.104

AC:

1096

AN:

10570

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10785

AN:

67918

Other (OTH)

AF:

0.104

AC:

220

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

759

1519

2278

3038

3797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.140

Hom.:

4102

Bravo

AF:

0.108

Asia WGS

AF:

0.0190

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:2

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

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

-0.90

CADD

Benign

3.8

(source)

DANN

Benign

0.60

PhyloP100

0.15

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