12-20815894-C-T

Position:

• chr12-20815894-C-T

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.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

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 -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/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.84+72C>T		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.84+72C>T		intron_variant			NP_001358026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.84+72C>T		intron_variant		2	NM_019844.4	ENSP00000370956	P1
SLCO1B3	ENST00000261196.6	c.84+72C>T		intron_variant		1		ENSP00000261196	P1
SLCO1B3	ENST00000540853.5	c.84+72C>T		intron_variant		1		ENSP00000442000

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

Gnomad4 AFR exome AF: 0.715

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.970

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.972

Gnomad4 OTH exome AF: 0.953

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

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.972

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.918

Alfa AF: 0.931 Hom.: 19257

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.83
CADD	Benign	5.1
DANN	Benign	0.50

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: rs10734710; hg19: chr12-20968828;