12-20916594-T-TA

Position:

• chr12-20916594-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019844.4(SLCO1B3):​c.*355dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7404 hom., cov: 0)
  • Exomes 𝑓: 0.21 (119 hom.)
• Consequence: SLCO1B3 NM_019844.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0160

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-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]

LOC124902894 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-20916594-T-TA is Benign according to our data. Variant chr12-20916594-T-TA is described in ClinVar as [Benign]. Clinvar id is 307921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.*355dupA		3_prime_UTR_variant	16/16	ENST00000381545.8	NP_062818.1
SLCO1B3	NM_001349920.2	c.*355dupA		3_prime_UTR_variant	14/14		NP_001336849.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1865+15135dupA		intron_variant			NP_001358026.1
LOC124902894	XM_047429949.1	c.-58+15135dupA		intron_variant			XP_047285905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.*355dupA		3_prime_UTR_variant	16/16	2	NM_019844.4	ENSP00000370956.4
SLCO1B3	ENST00000261196.6	c.*355dupA		3_prime_UTR_variant	14/14	1		ENSP00000261196.2
SLCO1B3-SLCO1B7	ENST00000540229.1	c.1865+15135dupA		intron_variant		2		ENSP00000441269.1
SLCO1B3-SLCO1B7	ENST00000381541.7	c.359+58031dupA		intron_variant		2		ENSP00000370952.3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46487 AN: 151622 Hom.: 7404 Cov.: 0

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.215 AC: 1075 AN: 5000 Hom.: 119 Cov.: 0 AF XY: 0.215 AC XY: 572 AN XY: 2666

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.306 AC: 46493 AN: 151734 Hom.: 7404 Cov.: 0 AF XY: 0.304 AC XY: 22557 AN XY: 74148

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.335

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rotor syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs397689574; hg19: chr12-21069528;