rs3764007

chr12-20861229-T-Achr12-20861229-T-Cchr12-20861229-T-G

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.481+91T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,166,428 control chromosomes in the GnomAD database, including 399,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (42510 hom., cov: 33)
  • Exomes 𝑓: 0.84 (356993 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510

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=-0.67).
• BP6: Variant 12-20861229-T-A is Benign according to our data. Variant chr12-20861229-T-A is described in ClinVar as [Benign]. Clinvar id is 1247275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.481+91T>A		intron_variant		ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.481+91T>A		intron_variant
SLCO1B3	NM_001349920.2	c.397+91T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.481+91T>A		intron_variant		2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.481+91T>A		intron_variant		1		P1
SLCO1B3	ENST00000540853.5	c.481+91T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110166 AN: 151968 Hom.: 42513 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.835 AC: 847044 AN: 1014342 Hom.: 356993 AF XY: 0.840 AC XY: 427738 AN XY: 509420

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.893

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.851

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.725 AC: 110190 AN: 152086 Hom.: 42510 Cov.: 33 AF XY: 0.724 AC XY: 53803 AN XY: 74348

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.781

Alfa AF: 0.684 Hom.: 2233

Bravo AF: 0.717

Asia WGS AF: 0.764 AC: 2655 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	-0.67
Cadd	Benign	9.1
Dann	Benign	0.86

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: rs3764007; hg19: chr12-21014163;