Genetic Variant SLCO1B1:c.85-7774A>G (chr12-21164876-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006446.5(SLCO1B1):c.85-7774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 476,994 control chromosomes in the GnomAD database, including 152,317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46671 hom., cov: 32)

Exomes 𝑓: 0.80 ( 105646 hom. )

Consequence

SLCO1B1
NM_006446.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.604

Publications

20 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:

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new If you want to explore the variant's impact on the transcript NM_006446.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 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.85-7774A>G		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.85-7774A>G	intron	N/A	ENSP00000256958.2	Q9Y6L6
SLCO1B1	ENST00000870182.1		c.85-7774A>G	intron	N/A	ENSP00000540241.1
SLCO1B1	ENST00000870184.1		c.85-7774A>G	intron	N/A	ENSP00000540243.1

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118869

AN:

151944

Hom.:

46628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.781

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.927

Gnomad FIN

AF:

0.693

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.778

Gnomad OTH

AF:

0.770

GnomAD2 exomes

AF:

0.800

AC:

136478

AN:

170684

AF XY:

0.805

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.807

Gnomad EAS exome

AF:

0.862

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.767

Gnomad OTH exome

AF:

0.777

GnomAD4 exome

AF:

0.804

AC:

261097

AN:

324932

Hom.:

105646

Cov.:

AF XY:

0.814

AC XY:

151067

AN XY:

185592

show subpopulations

African (AFR)

AF:

0.771

AC:

7104

AN:

9216

American (AMR)

AF:

0.805

AC:

23705

AN:

29458

Ashkenazi Jewish (ASJ)

AF:

0.806

AC:

8694

AN:

10784

East Asian (EAS)

AF:

0.857

AC:

10127

AN:

11810

South Asian (SAS)

AF:

0.921

AC:

55886

AN:

60708

European-Finnish (FIN)

AF:

0.696

AC:

10083

AN:

14480

Middle Eastern (MID)

AF:

0.749

AC:

2067

AN:

2760

European-Non Finnish (NFE)

AF:

0.771

AC:

131672

AN:

170694

Other (OTH)

AF:

0.783

AC:

11759

AN:

15022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

2243

4485

6728

8970

11213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.782

AC:

118970

AN:

152062

Hom.:

46671

Cov.:

AF XY:

0.782

AC XY:

58123

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.781

AC:

32408

AN:

41474

American (AMR)

AF:

0.784

AC:

11972

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

2828

AN:

3470

East Asian (EAS)

AF:

0.870

AC:

4500

AN:

5174

South Asian (SAS)

AF:

0.927

AC:

4474

AN:

4826

European-Finnish (FIN)

AF:

0.693

AC:

7334

AN:

10578

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.778

AC:

52852

AN:

67962

Other (OTH)

AF:

0.773

AC:

1632

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1332

2665

3997

5330

6662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.784

Hom.:

52401

Bravo

AF:

0.787

Asia WGS

AF:

0.888

AC:

3085

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.40

(source)

DANN

Benign

0.52

PhyloP100

-0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over