Genetic Variant SLCO1B1:p.Arg580Arg (chr12-21222355-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_006446.5(SLCO1B1):c.1738C>A(p.Arg580Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLCO1B1
NM_006446.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.885

Publications

31 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.885 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 link	c.1738C>A	p.Arg580Arg	synonymous_variant	Exon 13 of 15	ENST00000256958.3	NP_006437.3	Q9Y6L6Q05CV5A0A024RAU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3 link	c.1738C>A	p.Arg580Arg	synonymous_variant	Exon 13 of 15	1	NM_006446.5	ENSP00000256958.2		Q9Y6L6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

95994

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000551

AC:

AN:

181496

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000371

AC:

AN:

538492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

272170

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

12252

American (AMR)

AF:

0.00

AC:

AN:

22684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11174

East Asian (EAS)

AF:

0.00

AC:

AN:

14362

South Asian (SAS)

AF:

0.00

AC:

AN:

30826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1542

European-Non Finnish (NFE)

AF:

0.00000506

AC:

AN:

395020

Other (OTH)

AF:

0.00

AC:

AN:

20752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

95994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

43434

African (AFR)

AF:

0.00

AC:

AN:

23682

American (AMR)

AF:

0.00

AC:

AN:

6048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2990

East Asian (EAS)

AF:

0.00

AC:

AN:

3248

South Asian (SAS)

AF:

0.00

AC:

AN:

2910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52878

Other (OTH)

AF:

0.00

AC:

AN:

1222

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.1

(source)

DANN

Benign

0.72

PhyloP100

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

Other links and lift over