Genetic Variant SLCO1B1:c.85-237G>A (chr12-21172413-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.85-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,282 control chromosomes in the GnomAD database, including 60,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.89 ( 60473 hom., cov: 33)

Consequence

SLCO1B1
NM_006446.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.408

Publications

1 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=-0.91).

BP6

Variant 12-21172413-G-A is Benign according to our data. Variant chr12-21172413-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256789.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.85-237G>A		intron	N/A	NP_006437.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.85-237G>A	intron	N/A	ENSP00000256958.2	Q9Y6L6
SLCO1B1	ENST00000870182.1		c.85-237G>A	intron	N/A	ENSP00000540241.1
SLCO1B1	ENST00000870184.1		c.85-237G>A	intron	N/A	ENSP00000540243.1

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135523

AN:

152164

Hom.:

60435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.867

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.897

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.966

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.888

Gnomad OTH

AF:

0.894

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

GnomAD4 genome

AF:

0.891

AC:

135616

AN:

152282

Hom.:

60473

Cov.:

AF XY:

0.893

AC XY:

66487

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.866

AC:

35995

AN:

41548

American (AMR)

AF:

0.897

AC:

13723

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.938

AC:

3256

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5180

AN:

5186

South Asian (SAS)

AF:

0.966

AC:

4663

AN:

4826

European-Finnish (FIN)

AF:

0.886

AC:

9401

AN:

10608

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.888

AC:

60436

AN:

68022

Other (OTH)

AF:

0.895

AC:

1892

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

774

1547

2321

3094

3868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.884

Hom.:

8971

Bravo

AF:

0.890

Asia WGS

AF:

0.974

AC:

3384

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.75

(source)

DANN

Benign

0.23

PhyloP100

-0.41

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over