chr12-20861229-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	NM_019844.4	MANE Select	c.481+91T>A		intron	N/A	NP_062818.1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.481+91T>A		intron	N/A	NP_001358026.1
	SLCO1B3	NM_001349920.2		c.397+91T>A		intron	N/A	NP_001336849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.481+91T>A		intron	N/A	ENSP00000370956.4
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.481+91T>A		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.481+91T>A		intron	N/A	ENSP00000261196.2

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

African (AFR) AF: 0.403 AC: 9168 AN: 22772

American (AMR) AF: 0.804 AC: 17470 AN: 21730

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 14942 AN: 16740

East Asian (EAS) AF: 0.742 AC: 23969 AN: 32318

South Asian (SAS) AF: 0.907 AC: 51719 AN: 57048

European-Finnish (FIN) AF: 0.764 AC: 35121 AN: 45976

Middle Eastern (MID) AF: 0.872 AC: 3901 AN: 4476

European-Non Finnish (NFE) AF: 0.851 AC: 654822 AN: 769542

Other (OTH) AF: 0.821 AC: 35932 AN: 43740

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

African (AFR) AF: 0.435 AC: 18044 AN: 41448

American (AMR) AF: 0.812 AC: 12401 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3727 AN: 5180

South Asian (SAS) AF: 0.900 AC: 4340 AN: 4822

European-Finnish (FIN) AF: 0.747 AC: 7889 AN: 10566

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58017 AN: 68012

Other (OTH) AF: 0.781 AC: 1646 AN: 2108

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.1
DANN	Benign	0.86
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3764007; hg19: chr12-21014163;