rs78862986

Positions:

• chr12-20915981-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019844.4(SLCO1B3):​c.1866-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,544,480 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0098 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (255 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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]

LOC124902894 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1866-23C>T		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1865+14514C>T		intron_variant			NP_001358026.1
SLCO1B3	NM_001349920.2	c.1782-23C>T		intron_variant			NP_001336849.1
LOC124902894	XM_047429949.1	c.-58+14514C>T		intron_variant			XP_047285905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1866-23C>T		intron_variant		2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.1865+14514C>T		intron_variant		2		ENSP00000441269.1
SLCO1B3	ENST00000261196.6	c.1866-23C>T		intron_variant		1		ENSP00000261196.2
SLCO1B3-SLCO1B7	ENST00000381541.7	c.359+57410C>T		intron_variant		2		ENSP00000370952.3

Frequencies

GnomAD3 genomes AF: 0.00976 AC: 1483 AN: 151992 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.0151 AC: 3349 AN: 222334 Hom.: 108 AF XY: 0.0139 AC XY: 1679 AN XY: 120996

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.00127

Gnomad EAS exome AF: 0.0978

Gnomad SAS exome AF: 0.0183

Gnomad FIN exome AF: 0.000498

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.00951

GnomAD4 exome AF: 0.00516 AC: 7187 AN: 1392370 Hom.: 255 Cov.: 27 AF XY: 0.00534 AC XY: 3697 AN XY: 692378

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0335

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.0860

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.000539

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.00982 AC: 1494 AN: 152110 Hom.: 37 Cov.: 32 AF XY: 0.0105 AC XY: 778 AN XY: 74354

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0986

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.000568

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00576 Hom.: 0

Bravo AF: 0.0120

Asia WGS AF: 0.0650 AC: 227 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs78862986; hg19: chr12-21068915; COSMIC: COSV53938537;