rs3829311

Positions:

• chr12-20875159-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019844.4(SLCO1B3):​c.728-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,511,252 control chromosomes in the GnomAD database, including 474,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (36472 hom., cov: 31)
  • Exomes 𝑓: 0.80 (438433 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.497

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-20875159-T-C is Benign according to our data. Variant chr12-20875159-T-C is described in ClinVar as [Benign]. Clinvar id is 1225845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.728-76T>C		intron_variant		ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.728-76T>C		intron_variant
SLCO1B3	NM_001349920.2	c.644-76T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.728-76T>C		intron_variant		2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.728-76T>C		intron_variant		1		P1
SLCO1B3	ENST00000540853.5	c.728-76T>C		intron_variant		1
SLCO1B3	ENST00000544370.1	c.200-76T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100550 AN: 151932 Hom.: 36476 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.797 AC: 1083801 AN: 1359198 Hom.: 438433 AF XY: 0.801 AC XY: 544855 AN XY: 680558

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.844

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.661 AC: 100557 AN: 152054 Hom.: 36472 Cov.: 31 AF XY: 0.657 AC XY: 48830 AN XY: 74330

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.712

Alfa AF: 0.671 Hom.: 5311

Bravo AF: 0.654

Asia WGS AF: 0.650 AC: 2259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.32

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: rs3829311; hg19: chr12-21028093; COSMIC: COSV53938168;