chr12-20855146-T-TAATTG

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_019844.4(SLCO1B3):c.205_209dupATTGA(p.Asp70GlufsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,609,310 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0038 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 27 hom. )

Consequence

SLCO1B3
NM_019844.4 frameshift

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:2

Conservation

PhyloP100: -0.751

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 7 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 link	c.205_209dupATTGA	p.Asp70GlufsTer13	frameshift_variant	Exon 4 of 16	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 link	c.205_209dupATTGA	p.Asp70GlufsTer13	frameshift_variant	Exon 2 of 16		NP_001358026.1
SLCO1B3	NM_001349920.2 link	c.121_125dupATTGA	p.Asp42GlufsTer13	frameshift_variant	Exon 2 of 14		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 link	c.205_209dupATTGA	p.Asp70GlufsTer13	frameshift_variant	Exon 4 of 16	2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 link	c.205_209dupATTGA	p.Asp70GlufsTer13	frameshift_variant	Exon 2 of 16	2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.00380

AC:

579

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00463

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00416

AC:

1024

AN:

245910

AF XY:

0.00409

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.00600

GnomAD4 exome

AF:

0.00348

AC:

5072

AN:

1456956

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

2518

AN XY:

724844

show subpopulations

Gnomad4 AFR exome

AF:

0.000513

AC:

AN:

33148

Gnomad4 AMR exome

AF:

0.000344

AC:

AN:

43556

Gnomad4 ASJ exome

AF:

0.00115

AC:

AN:

25982

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39648

Gnomad4 SAS exome

AF:

0.000129

AC:

AN:

85544

Gnomad4 FIN exome

AF:

0.0227

AC:

1208

AN:

53294

Gnomad4 NFE exome

AF:

0.00325

AC:

3610

AN:

1110242

Gnomad4 Remaining exome

AF:

0.00299

AC:

180

AN:

60214

Heterozygous variant carriers

210

421

631

842

1052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00380

AC:

579

AN:

152354

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000745

AC:

0.000745407

AN:

0.000745407

Gnomad4 AMR

AF:

0.00137

AC:

0.00137201

AN:

0.00137201

Gnomad4 ASJ

AF:

0.000576

AC:

0.000576037

AN:

0.000576037

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000206868

AN:

0.000206868

Gnomad4 FIN

AF:

0.0190

AC:

0.0190171

AN:

0.0190171

Gnomad4 NFE

AF:

0.00463

AC:

0.00463017

AN:

0.00463017

Gnomad4 OTH

AF:

0.00331

AC:

0.00331126

AN:

0.00331126

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

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

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00237

EpiCase

AF:

0.00278

EpiControl

AF:

0.00268

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Rotor syndrome

Pathogenic:1Uncertain:1

May 28, 2019

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The SLCO1B3 c.205_209dup; p.Asp70GlufsTer13 variant (rs558592800, ClinVar Variation ID: 712105) is reported in the literature as one among several variants in one family with autism spectrum disorder, but with no details on hemolytic anemia or related phenotype (Yuen 2015). This variant is found in the Finnish European population with an allele frequency of 2.0% (499/24964 alleles, including 8 homozygotes) in the Genome Aggregation Database (v2.1.1). This variant causes a frameshift by inserting 5 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Since the mechanism of pathogenicity for SLCO1B3 is by loss-of-function, this variant is considered to be pathogenic. References: Yuen RK et al., Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med. 2015 Feb;21(2):185-91. PMID: 25621899. -

not provided

Benign:1

Nov 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SLCO1B3-related disorder

Benign:1

Sep 01, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=31/169

disease causing (fs/PTC)

Splicing

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