dbSNP rs3764006: SLCO1B3:p.Gly611Gly (chr12-20901435-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019844.4(SLCO1B3):c.1833G>A(p.Gly611Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 1,561,636 control chromosomes in the GnomAD database, including 582,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G611G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.71 ( 42957 hom., cov: 32)

Exomes 𝑓: 0.87 ( 539240 hom. )

Consequence

SLCO1B3
NM_019844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.38

Publications

31 publications found

Variant links:

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) 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 endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

SLCO1B3 links:

SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

SLCO1B3-SLCO1B7 links:

LOC124902894 (HGNC:):

LOC124902894 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-20901435-G-A is Benign according to our data. Variant chr12-20901435-G-A is described in ClinVar as Benign. ClinVar VariationId is 440286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLCO1B3	NM_019844.4	MANE Select	c.1833G>A	p.Gly611Gly	synonymous	Exon 15 of 16	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1		c.1833G>A	p.Gly611Gly	synonymous	Exon 13 of 16	NP_001358026.1
SLCO1B3	NM_001349920.2		c.1749G>A	p.Gly583Gly	synonymous	Exon 13 of 14	NP_001336849.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.1833G>A	p.Gly611Gly	synonymous	Exon 15 of 16	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1833G>A	p.Gly611Gly	synonymous	Exon 13 of 16	ENSP00000441269.1
SLCO1B3	ENST00000261196.6	TSL:1	c.1833G>A	p.Gly611Gly	synonymous	Exon 13 of 14	ENSP00000261196.2

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108446

AN:

151900

Hom.:

42953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.900

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.760

GnomAD2 exomes

AF:

0.817

AC:

171302

AN:

209728

AF XY:

0.836

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.765

Gnomad ASJ exome

AF:

0.893

Gnomad EAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.776

Gnomad NFE exome

AF:

0.885

Gnomad OTH exome

AF:

0.837

GnomAD4 exome

AF:

0.870

AC:

1225839

AN:

1409618

Hom.:

539240

Cov.:

AF XY:

0.873

AC XY:

611656

AN XY:

700460

show subpopulations

African (AFR)

AF:

0.317

AC:

9683

AN:

30584

American (AMR)

AF:

0.761

AC:

24513

AN:

32220

Ashkenazi Jewish (ASJ)

AF:

0.898

AC:

22030

AN:

24526

East Asian (EAS)

AF:

0.771

AC:

29083

AN:

37698

South Asian (SAS)

AF:

0.936

AC:

70793

AN:

75656

European-Finnish (FIN)

AF:

0.784

AC:

41566

AN:

53008

Middle Eastern (MID)

AF:

0.886

AC:

4810

AN:

5426

European-Non Finnish (NFE)

AF:

0.892

AC:

973884

AN:

1092180

Other (OTH)

AF:

0.848

AC:

49477

AN:

58320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

6980

13959

20939

27918

34898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20970

41940

62910

83880

104850

<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:

0.714

AC:

108481

AN:

152018

Hom.:

42957

Cov.:

AF XY:

0.712

AC XY:

52881

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.341

AC:

14128

AN:

41400

American (AMR)

AF:

0.762

AC:

11639

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

3108

AN:

3472

East Asian (EAS)

AF:

0.763

AC:

3938

AN:

5164

South Asian (SAS)

AF:

0.938

AC:

4524

AN:

4824

European-Finnish (FIN)

AF:

0.769

AC:

8129

AN:

10568

Middle Eastern (MID)

AF:

0.861

AC:

253

AN:

294

European-Non Finnish (NFE)

AF:

0.887

AC:

60332

AN:

67996

Other (OTH)

AF:

0.763

AC:

1611

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1155

2310

3464

4619

5774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.836

Hom.:

252078

Bravo

AF:

0.697

Asia WGS

AF:

0.797

AC:

2770

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Rotor syndrome (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.65

(source)

DANN

Benign

0.86

PhyloP100

-1.4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over