NM_019844.4:c.481+91T>A

Variant names:

• chr12-20861229-T-A
• rs3764007
• NM_019844.4:c.481+91T>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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: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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.481+91T>A		intron_variant	Intron 6 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.481+91T>A		intron_variant	Intron 4 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.397+91T>A		intron_variant	Intron 4 of 13		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.481+91T>A		intron_variant	Intron 6 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.481+91T>A		intron_variant	Intron 4 of 15	2		ENSP00000441269.1

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;