dbSNP rs4149046: SLCO1B1:c.481+191G>A (chr12-21177088-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006446.5(SLCO1B1):c.481+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,966 control chromosomes in the GnomAD database, including 11,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 11918 hom., cov: 33)

Consequence

SLCO1B1
NM_006446.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.843

Publications

6 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 12-21177088-G-A is Benign according to our data. Variant chr12-21177088-G-A is described in ClinVar as Benign. ClinVar VariationId is 1295257.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 link	c.481+191G>A		intron_variant	Intron 5 of 14	ENST00000256958.3	NP_006437.3	Q9Y6L6Q05CV5A0A024RAU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3 link	c.481+191G>A		intron_variant	Intron 5 of 14	1	NM_006446.5	ENSP00000256958.2		Q9Y6L6
ENSG00000257062	ENST00000543498.5 link	n.*454G>A		downstream_gene_variant		4		ENSP00000454306.1		H3BMA8

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54688

AN:

151848

Hom.:

11916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.381

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.360

AC:

54694

AN:

151966

Hom.:

11918

Cov.:

AF XY:

0.360

AC XY:

26700

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.105

AC:

4359

AN:

41504

American (AMR)

AF:

0.426

AC:

6502

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1652

AN:

3466

East Asian (EAS)

AF:

0.252

AC:

1304

AN:

5166

South Asian (SAS)

AF:

0.450

AC:

2167

AN:

4816

European-Finnish (FIN)

AF:

0.433

AC:

4561

AN:

10544

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33044

AN:

67904

Other (OTH)

AF:

0.381

AC:

801

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1612

3224

4836

6448

8060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.445

Hom.:

26309

Bravo

AF:

0.348

Asia WGS

AF:

0.316

AC:

1097

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.90

(source)

DANN

Benign

0.46

PhyloP100

-0.84

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over