12-20902672-G-C

Variant names:

• chr12-20902672-G-C
• rs4762803
• NM_019844.4:c.1865+1205G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1865+1205G>C		intron_variant	Intron 15 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1865+1205G>C		intron_variant	Intron 13 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.1781+1205G>C		intron_variant	Intron 13 of 13		NP_001336849.1
LOC124902894	XM_047429949.1	c.-58+1205G>C		intron_variant	Intron 1 of 9		XP_047285905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1865+1205G>C		intron_variant	Intron 15 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.1865+1205G>C		intron_variant	Intron 13 of 15	2		ENSP00000441269.1
SLCO1B3	ENST00000261196.6	c.1865+1205G>C		intron_variant	Intron 13 of 13	1		ENSP00000261196.2
SLCO1B3-SLCO1B7	ENST00000381541.7	c.359+44101G>C		intron_variant	Intron 3 of 13	2		ENSP00000370952.3

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

African (AFR) AF: 0.344 AC: 14235 AN: 41402

American (AMR) AF: 0.762 AC: 11639 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3106 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3933 AN: 5162

South Asian (SAS) AF: 0.938 AC: 4530 AN: 4828

European-Finnish (FIN) AF: 0.770 AC: 8122 AN: 10554

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60372 AN: 68032

Other (OTH) AF: 0.763 AC: 1613 AN: 2114

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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4762803; hg19: chr12-21055606;