rs71583718

Positions:

• chr12-20862930-C-G

Variant summary

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

The NM_019844.4(SLCO1B3):​c.727+76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 750,380 control chromosomes in the GnomAD database, including 1,181 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 0.043 (227 hom., cov: 32)
  • Exomes 𝑓: 0.043 (954 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.727+76C>G		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.727+76C>G		intron_variant			NP_001358026.1
SLCO1B3	NM_001349920.2	c.643+76C>G		intron_variant			NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.727+76C>G		intron_variant		2	NM_019844.4	ENSP00000370956	P1
SLCO1B3	ENST00000261196.6	c.727+76C>G		intron_variant		1		ENSP00000261196	P1
SLCO1B3	ENST00000540853.5	c.727+76C>G		intron_variant		1		ENSP00000442000
SLCO1B3	ENST00000544370.1	c.199+76C>G		intron_variant		5		ENSP00000443225

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6607 AN: 152076 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0432 AC: 25831 AN: 598186 Hom.: 954 AF XY: 0.0423 AC XY: 13361 AN XY: 316016

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.0736

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.0359

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.0434 AC: 6609 AN: 152194 Hom.: 227 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74410

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.0316

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0357 Hom.: 12

Bravo AF: 0.0412

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.024
DANN	Benign	0.37

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: rs71583718; hg19: chr12-21015864; COSMIC: COSV53940318; COSMIC: COSV53940318;