12-21334049-T-G

Position:

• chr12-21334049-T-G

Variant summary

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

The NM_001386879.1(SLCO1A2):​c.60+539A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,026 control chromosomes in the GnomAD database, including 870 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 0.091 (870 hom., cov: 33)
• Consequence: SLCO1A2 NM_001386879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1A2	NM_001386879.1	c.60+539A>C		intron_variant		ENST00000683939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1A2	ENST00000683939.1	c.60+539A>C		intron_variant			NM_001386879.1	P1

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13778 AN: 151908 Hom.: 870 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0906 AC: 13768 AN: 152026 Hom.: 870 Cov.: 33 AF XY: 0.0879 AC XY: 6535 AN XY: 74304

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.103

Alfa AF: 0.103 Hom.: 118

Bravo AF: 0.0883

Asia WGS AF: 0.0240 AC: 82 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.60

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: rs11045981; hg19: chr12-21486983;