rs12818993

Positions:

• chr12-21389013-G-A
• chr12-21389013-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134431.5(SLCO1A2):​c.-190+5893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,162 control chromosomes in the GnomAD database, including 1,132 homozygotes. 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: 𝑓 0.11 (1132 hom., cov: 32)
• Consequence: SLCO1A2 NM_134431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1A2	NM_001386878.1	c.-63+14406C>T		intron_variant			NP_001373807.1
SLCO1A2	NM_001386881.1	c.-58+28869C>T		intron_variant			NP_001373810.1
SLCO1A2	NM_134431.5	c.-190+5893C>T		intron_variant			NP_602307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-190+5893C>T		intron_variant		1		ENSP00000305974.6
SLCO1A2	ENST00000453443.5	c.-63+14406C>T		intron_variant		3		ENSP00000409314.1
SLCO1A2	ENST00000450590.5	c.-58+14406C>T		intron_variant		4		ENSP00000407462.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16491 AN: 152044 Hom.: 1136 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.108 AC: 16491 AN: 152162 Hom.: 1132 Cov.: 32 AF XY: 0.111 AC XY: 8256 AN XY: 74388

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0914 Hom.: 818

Bravo AF: 0.104

Asia WGS AF: 0.230 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.41

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: rs12818993; hg19: chr12-21541947;