chr12-20861014-C-A

Variant names:

• chr12-20861014-C-A
• rs3764009
• NM_019844.4:c.360-3C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019844.4(SLCO1B3):​c.360-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLCO1B3 NM_019844.4 splice_region, intron
• Scores: Splicing: ADA: 0.4610
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.360-3C>A		splice_region intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.360-3C>A		splice_region intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.276-3C>A		splice_region 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.360-3C>A		splice_region intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.360-3C>A		splice_region intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.360-3C>A		splice_region intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1407106 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700730

African (AFR) AF: 0.00 AC: 0 AN: 31434

American (AMR) AF: 0.00 AC: 0 AN: 36196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 38250

South Asian (SAS) AF: 0.00 AC: 0 AN: 79308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079904

Other (OTH) AF: 0.00 AC: 0 AN: 58384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.67
PhyloP100		-0.44

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.46
dbscSNV1_RF	Benign	0.41
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3764009; hg19: chr12-21013948;