chr12-20815710-AATATTCACTTGGTATCTG-A

Variant names:

• chr12-20815710-AATATTCACTTGGTATCTG-A
• rs527574443
• NM_019844.4:c.-28_-11delATATTCACTTGGTATCTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_019844.4(SLCO1B3):​c.-28_-11delATATTCACTTGGTATCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,469,848 control chromosomes in the GnomAD database, including 54,843 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4628 hom., cov: 23)
  • Exomes 𝑓: 0.27 (50215 hom.)
• Consequence: SLCO1B3 NM_019844.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.607
• Publications: 1 publications found

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:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-20815710-AATATTCACTTGGTATCTG-A is Benign according to our data. Variant chr12-20815710-AATATTCACTTGGTATCTG-A is described in ClinVar as [Benign]. Clinvar id is 993345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.-28_-11delATATTCACTTGGTATCTG		5_prime_UTR_variant	Exon 3 of 16	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.-28_-11delATATTCACTTGGTATCTG		5_prime_UTR_variant	Exon 1 of 16		NP_001358026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.-28_-11delATATTCACTTGGTATCTG		5_prime_UTR_variant	Exon 3 of 16	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.-28_-11delATATTCACTTGGTATCTG		5_prime_UTR_variant	Exon 1 of 16	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35565 AN: 152042 Hom.: 4629 Cov.: 23

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.140 AC: 29724 AN: 212094 AF XY: 0.149

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.0686

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.0765

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.272 AC: 358538 AN: 1317686 Hom.: 50215 AF XY: 0.269 AC XY: 177123 AN XY: 659148

African (AFR) AF: 0.124 AC: 3728 AN: 29980

American (AMR) AF: 0.147 AC: 6057 AN: 41130

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 5886 AN: 24282

East Asian (EAS) AF: 0.156 AC: 5959 AN: 38166

South Asian (SAS) AF: 0.133 AC: 10163 AN: 76700

European-Finnish (FIN) AF: 0.239 AC: 12184 AN: 51072

Middle Eastern (MID) AF: 0.380 AC: 1980 AN: 5204

European-Non Finnish (NFE) AF: 0.299 AC: 298015 AN: 996158

Other (OTH) AF: 0.265 AC: 14566 AN: 54994

GnomAD4 genome AF: 0.234 AC: 35591 AN: 152162 Hom.: 4628 Cov.: 23 AF XY: 0.230 AC XY: 17135 AN XY: 74404

African (AFR) AF: 0.135 AC: 5619 AN: 41534

American (AMR) AF: 0.221 AC: 3373 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3472

East Asian (EAS) AF: 0.169 AC: 878 AN: 5188

South Asian (SAS) AF: 0.161 AC: 775 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2691 AN: 10568

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20363 AN: 67976

Other (OTH) AF: 0.262 AC: 553 AN: 2114

Alfa AF: 0.223 Hom.: 843

Asia WGS AF: 0.161 AC: 557 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Rotor syndrome Benign:1

Nov 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs527574443; hg19: chr12-20968644; COSMIC: COSV53933007;