12-21239638-A-C

Position:

• chr12-21239638-A-C

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.*449A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,168 control chromosomes in the GnomAD database, including 1,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1529 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113

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]

LOC124902895 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-21239638-A-C is Benign according to our data. Variant chr12-21239638-A-C is described in ClinVar as [Benign]. Clinvar id is 307968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.*449A>C		3_prime_UTR_variant	15/15	ENST00000256958.3	NP_006437.3
LOC124902895	XR_007063239.1	n.87-5339T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.*449A>C		3_prime_UTR_variant	15/15	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18502 AN: 152050 Hom.: 1532 Cov.: 33

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0773

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.122 AC: 18496 AN: 152168 Hom.: 1529 Cov.: 33 AF XY: 0.116 AC XY: 8645 AN XY: 74396

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0777

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0799 Hom.: 161

Bravo AF: 0.119

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rotor syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045891; hg19: chr12-21392572;