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:):

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
LOC124902894	XM_047429949.1	c.-58+14514C>T		intron_variant			XP_047285905.1
SLCO1B3	NM_001349920.2	c.1782-23C>T		intron_variant			NP_001336849.1

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	P1
SLCO1B3	ENST00000261196.6	c.1866-23C>T		intron_variant		1		ENSP00000261196	P1

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;