NM_006446.5:c.-3A>T

Variant names:

• chr12-21141572-A-T
• rs180888034
• NM_006446.5:c.-3A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006446.5(SLCO1B1):​c.-3A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLCO1B1 NM_006446.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.-3A>T		5_prime_UTR	Exon 2 of 15	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.-3A>T		5_prime_UTR	Exon 2 of 15	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.-3A>T		5_prime_UTR	Exon 3 of 16	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.-3A>T		5_prime_UTR	Exon 3 of 16	ENSP00000540243.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250474 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448064 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 721274

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39374

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100624

Other (OTH) AF: 0.00 AC: 0 AN: 59790

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		0.19

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: rs180888034; hg19: chr12-21294506;