chr12-20858647-G-A

Variant names:

• chr12-20858647-G-A
• rs4149118
• NM_019844.4:c.359+76G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019844.4(SLCO1B3):​c.359+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,384,570 control chromosomes in the GnomAD database, including 296,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (24387 hom., cov: 31)
  • Exomes 𝑓: 0.66 (271907 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.193
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-20858647-G-A is Benign according to our data. Variant chr12-20858647-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	NM_019844.4	MANE Select	c.359+76G>A		intron	N/A	NP_062818.1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.359+76G>A		intron	N/A	NP_001358026.1
	SLCO1B3	NM_001349920.2		c.275+76G>A		intron	N/A	NP_001336849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.359+76G>A		intron	N/A	ENSP00000370956.4
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.359+76G>A		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.359+76G>A		intron	N/A	ENSP00000261196.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81425 AN: 151444 Hom.: 24387 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.659 AC: 812740 AN: 1233006 Hom.: 271907 AF XY: 0.663 AC XY: 409835 AN XY: 617812

African (AFR) AF: 0.231 AC: 6526 AN: 28274

American (AMR) AF: 0.635 AC: 21470 AN: 33810

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 13919 AN: 20816

East Asian (EAS) AF: 0.559 AC: 21378 AN: 38268

South Asian (SAS) AF: 0.776 AC: 53923 AN: 69448

European-Finnish (FIN) AF: 0.569 AC: 28021 AN: 49266

Middle Eastern (MID) AF: 0.571 AC: 2914 AN: 5104

European-Non Finnish (NFE) AF: 0.675 AC: 631742 AN: 935930

Other (OTH) AF: 0.631 AC: 32847 AN: 52090

GnomAD4 genome AF: 0.537 AC: 81431 AN: 151564 Hom.: 24387 Cov.: 31 AF XY: 0.538 AC XY: 39838 AN XY: 74072

African (AFR) AF: 0.251 AC: 10333 AN: 41148

American (AMR) AF: 0.607 AC: 9257 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2333 AN: 3468

East Asian (EAS) AF: 0.538 AC: 2776 AN: 5160

South Asian (SAS) AF: 0.767 AC: 3695 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5803 AN: 10518

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45315 AN: 67902

Other (OTH) AF: 0.562 AC: 1184 AN: 2108

Alfa AF: 0.629 Hom.: 99027

Bravo AF: 0.527

Asia WGS AF: 0.611 AC: 2117 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.87
PhyloP100		-0.19
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: rs4149118; hg19: chr12-21011581; COSMIC: COSV53936619; COSMIC: COSV53936619;