chr12-21141292-AATTT-A

Variant names:

• chr12-21141292-AATTT-A
• rs4149092
• NM_006446.5:c.-61-217_-61-214delATTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006446.5(SLCO1B1):​c.-61-217_-61-214delATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 151,800 control chromosomes in the GnomAD database, including 274 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (274 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

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]

SLCO1B1 Gene-Disease associations (from GenCC):

• Rotor syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-21141292-AATTT-A is Benign according to our data. Variant chr12-21141292-AATTT-A is described in ClinVar as Benign. ClinVar VariationId is 1225618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006446.5. 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
	SLCO1B1	NM_006446.5	MANE Select	c.-61-217_-61-214delATTT		intron	N/A	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.-61-217_-61-214delATTT		intron	N/A	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870189.1		c.-278_-275delATTT		5_prime_UTR	Exon 1 of 14	ENSP00000540248.1
	SLCO1B1	ENST00000870182.1		c.-61-217_-61-214delATTT		intron	N/A	ENSP00000540241.1

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7569 AN: 151682 Hom.: 274 Cov.: 31

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0662

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

GnomAD4 genome AF: 0.0499 AC: 7571 AN: 151800 Hom.: 274 Cov.: 31 AF XY: 0.0517 AC XY: 3836 AN XY: 74194

African (AFR) AF: 0.0125 AC: 520 AN: 41504

American (AMR) AF: 0.0362 AC: 552 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3464

East Asian (EAS) AF: 0.127 AC: 657 AN: 5158

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4816

European-Finnish (FIN) AF: 0.108 AC: 1140 AN: 10550

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0594 AC: 4026 AN: 67756

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0288 Hom.: 22

Asia WGS AF: 0.0680 AC: 236 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
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: rs4149092; hg19: chr12-21294226;