chr12-21172413-G-A

Position:

• chr12-21172413-G-A

Variant summary

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

The NM_006446.5(SLCO1B1):​c.85-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,282 control chromosomes in the GnomAD database, including 60,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60473 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.408

Genes affected

SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) 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 numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-21172413-G-A is Benign according to our data. Variant chr12-21172413-G-A is described in ClinVar as [Benign]. Clinvar id is 1256789.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21172413-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B1	NM_006446.5	c.85-237G>A		intron_variant		ENST00000256958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.85-237G>A		intron_variant		1	NM_006446.5	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135523 AN: 152164 Hom.: 60435 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.891 AC: 135616 AN: 152282 Hom.: 60473 Cov.: 33 AF XY: 0.893 AC XY: 66487 AN XY: 74452

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.895

Alfa AF: 0.885 Hom.: 8681

Bravo AF: 0.890

Asia WGS AF: 0.974 AC: 3384 AN: 3474

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	-0.91
CADD	Benign	0.75
DANN	Benign	0.23

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: rs7295464; hg19: chr12-21325347;