12-20902672-G-C

Position:

• chr12-20902672-G-C

Variant summary

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

The NM_019844.4(SLCO1B3):​c.1865+1205G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,036 control chromosomes in the GnomAD database, including 43,025 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 0.71 (43025 hom., cov: 31)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1865+1205G>C		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1865+1205G>C		intron_variant			NP_001358026.1
LOC124902894	XM_047429949.1	c.-58+1205G>C		intron_variant			XP_047285905.1
SLCO1B3	NM_001349920.2	c.1781+1205G>C		intron_variant			NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1865+1205G>C		intron_variant		2	NM_019844.4	ENSP00000370956	P1
SLCO1B3	ENST00000261196.6	c.1865+1205G>C		intron_variant		1		ENSP00000261196	P1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108587 AN: 151918 Hom.: 43020 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.714 AC: 108622 AN: 152036 Hom.: 43025 Cov.: 31 AF XY: 0.712 AC XY: 52935 AN XY: 74300

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.763

Alfa AF: 0.699 Hom.: 2498

Bravo AF: 0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.14
DANN	Benign	0.48

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: rs4762803; hg19: chr12-21055606;