Variant chr12-20813517-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_019844.4(SLCO1B3):c.-180-7T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 152,262 control chromosomes in the GnomAD database, including 103 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 0.037 ( 103 hom., cov: 32)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

SLCO1B3
NM_019844.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009557

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.162

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 12-20813517-T-G is Benign according to our data. Variant chr12-20813517-T-G is described in ClinVar as [Benign]. Clinvar id is 307882.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4 linkuse as main transcript	c.-180-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000381545.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.-180-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_019844.4	P1	Q9NPD5-1
SLCO1B3	ENST00000540853.5 linkuse as main transcript	c.-65-2157T>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5631

AN:

152132

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0749

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0469

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.0370

AC:

5626

AN:

152250

Hom.:

103

Cov.:

AF XY:

0.0366

AC XY:

2726

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.0381

Gnomad4 ASJ

AF:

0.0455

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0748

Gnomad4 FIN

AF:

0.0265

Gnomad4 NFE

AF:

0.0398

Gnomad4 OTH

AF:

0.0469

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0368

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000096

dbscSNV1_RF

Benign

0.052

SpliceAI score (max)

0.11

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