chr12-20815894-C-T

Variant names:

• chr12-20815894-C-T
• rs10734710
• NM_019844.4:c.84+72C>T

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.84+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 844,514 control chromosomes in the GnomAD database, including 385,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (63027 hom., cov: 32)
  • Exomes 𝑓: 0.96 (322416 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.447
• Publications: 5 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=-0.83).
• BP6: Variant 12-20815894-C-T is Benign according to our data. Variant chr12-20815894-C-T is described in ClinVar as [Benign]. Clinvar id is 1274436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.84+72C>T		intron_variant	Intron 3 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.84+72C>T		intron_variant	Intron 1 of 15		NP_001358026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.84+72C>T		intron_variant	Intron 3 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.84+72C>T		intron_variant	Intron 1 of 15	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137499 AN: 152122 Hom.: 62982 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.917

GnomAD4 exome AF: 0.964 AC: 667434 AN: 692274 Hom.: 322416 AF XY: 0.964 AC XY: 349219 AN XY: 362188

African (AFR) AF: 0.715 AC: 11582 AN: 16206

American (AMR) AF: 0.965 AC: 22606 AN: 23424

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 16683 AN: 17202

East Asian (EAS) AF: 0.993 AC: 32656 AN: 32902

South Asian (SAS) AF: 0.954 AC: 47910 AN: 50214

European-Finnish (FIN) AF: 0.969 AC: 39068 AN: 40334

Middle Eastern (MID) AF: 0.919 AC: 3672 AN: 3996

European-Non Finnish (NFE) AF: 0.972 AC: 461630 AN: 474806

Other (OTH) AF: 0.953 AC: 31627 AN: 33190

GnomAD4 genome AF: 0.904 AC: 137598 AN: 152240 Hom.: 63027 Cov.: 32 AF XY: 0.907 AC XY: 67479 AN XY: 74430

African (AFR) AF: 0.734 AC: 30475 AN: 41510

American (AMR) AF: 0.954 AC: 14582 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3376 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5135 AN: 5176

South Asian (SAS) AF: 0.947 AC: 4569 AN: 4824

European-Finnish (FIN) AF: 0.967 AC: 10261 AN: 10616

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66103 AN: 68040

Other (OTH) AF: 0.918 AC: 1939 AN: 2112

Alfa AF: 0.946 Hom.: 33237

Bravo AF: 0.895

Asia WGS AF: 0.956 AC: 3303 AN: 3458

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	-0.83
CADD	Benign	5.1
DANN	Benign	0.50
PhyloP100		0.45
PromoterAI		0.012	Neutral
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: rs10734710; hg19: chr12-20968828;