12-20862972-C-G

Variant names:

• chr12-20862972-C-G
• rs17680137
• NM_019844.4:c.727+118C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019844.4(SLCO1B3):​c.727+118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 515,374 control chromosomes in the GnomAD database, including 4,654 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 0.10 (1126 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3528 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	NM_019844.4	MANE Select	c.727+118C>G		intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.727+118C>G		intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.643+118C>G		intron	N/A	NP_001336849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.727+118C>G		intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.727+118C>G		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.727+118C>G		intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15917 AN: 152012 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.127 AC: 46083 AN: 363246 Hom.: 3528 AF XY: 0.128 AC XY: 24214 AN XY: 189904

African (AFR) AF: 0.0282 AC: 284 AN: 10080

American (AMR) AF: 0.0829 AC: 1034 AN: 12476

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 2096 AN: 10752

East Asian (EAS) AF: 0.000230 AC: 6 AN: 26118

South Asian (SAS) AF: 0.0653 AC: 1184 AN: 18132

European-Finnish (FIN) AF: 0.101 AC: 3528 AN: 34816

Middle Eastern (MID) AF: 0.248 AC: 556 AN: 2238

European-Non Finnish (NFE) AF: 0.152 AC: 34606 AN: 227650

Other (OTH) AF: 0.133 AC: 2789 AN: 20984

GnomAD4 genome AF: 0.105 AC: 15912 AN: 152128 Hom.: 1126 Cov.: 32 AF XY: 0.100 AC XY: 7448 AN XY: 74382

African (AFR) AF: 0.0291 AC: 1208 AN: 41510

American (AMR) AF: 0.109 AC: 1664 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4826

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10584

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.153 AC: 10429 AN: 67968

Other (OTH) AF: 0.136 AC: 287 AN: 2116

Alfa AF: 0.120 Hom.: 158

Bravo AF: 0.104

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.70
PhyloP100		-2.1
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: rs17680137; hg19: chr12-21015906; COSMIC: COSV53945888; COSMIC: COSV53945888;