chr12-20861014-C-T

Position:

chr12-20861014-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019844.4(SLCO1B3):c.360-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,552,940 control chromosomes in the GnomAD database, including 540,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 42467 hom., cov: 31)

Exomes 𝑓: 0.84 ( 497926 hom. )

Consequence

SLCO1B3
NM_019844.4 splice_region, intron

Scores

Splicing: ADA: 0.0002759

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.436

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:

SLCO1B3 (HGNC:):

SLCO1B3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-20861014-C-T is Benign according to our data. Variant chr12-20861014-C-T is described in ClinVar as [Benign]. Clinvar id is 261185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-20861014-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 linkuse as main transcript	c.360-3C>T	splice_region_variant, intron_variant	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.360-3C>T	splice_region_variant, intron_variant		NP_001358026.1
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.276-3C>T	splice_region_variant, intron_variant		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.360-3C>T		splice_region_variant, intron_variant		2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 linkuse as main transcript	c.360-3C>T		splice_region_variant, intron_variant		2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110072

AN:

151836

Hom.:

42470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.720

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.781

GnomAD3 exomes

AF:

0.803

AC:

177645

AN:

221244

Hom.:

72859

AF XY:

0.818

AC XY:

98277

AN XY:

120096

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.789

Gnomad ASJ exome

AF:

0.889

Gnomad EAS exome

AF:

0.715

Gnomad SAS exome

AF:

0.902

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.852

Gnomad OTH exome

AF:

0.826

GnomAD4 exome

AF:

0.839

AC:

1175711

AN:

1400986

Hom.:

497926

Cov.:

AF XY:

0.843

AC XY:

588204

AN XY:

697890

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.893

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.906

Gnomad4 FIN exome

AF:

0.762

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.824

GnomAD4 genome

AF:

0.725

AC:

110096

AN:

151954

Hom.:

42467

Cov.:

AF XY:

0.724

AC XY:

53732

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.899

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.853

Gnomad4 OTH

AF:

0.780

Alfa

AF:

0.821

Hom.:

57967

Bravo

AF:

0.717

Asia WGS

AF:

0.764

AC:

2655

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over