chr12-20855422-T-G

Position:

• chr12-20855422-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019844.4(SLCO1B3):​c.226+253T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,998 control chromosomes in the GnomAD database, including 42,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (42477 hom., cov: 31)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 12-20855422-T-G is Benign according to our data. Variant chr12-20855422-T-G is described in ClinVar as [Benign]. Clinvar id is 1252625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.226+253T>G		intron_variant		ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.226+253T>G		intron_variant
SLCO1B3	NM_001349920.2	c.142+253T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.226+253T>G		intron_variant		2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.226+253T>G		intron_variant		1		P1
SLCO1B3	ENST00000540853.5	c.226+253T>G		intron_variant		1
SLCO1B3	ENST00000545880.1	n.78+253T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110084 AN: 151880 Hom.: 42480 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.724 AC: 110108 AN: 151998 Hom.: 42477 Cov.: 31 AF XY: 0.724 AC XY: 53744 AN XY: 74276

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.779

Alfa AF: 0.762 Hom.: 5681

Bravo AF: 0.717

Asia WGS AF: 0.764 AC: 2654 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.062
DANN	Benign	0.49

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: rs4149109; hg19: chr12-21008356;