chr12-21334049-T-G

Variant names:

• chr12-21334049-T-G
• rs11045981
• NM_001386879.1:c.60+539A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLCO1A2	NM_001386879.1	c.60+539A>C		intron_variant	Intron 2 of 14	ENST00000683939.1	NP_001373808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000683939.1	c.60+539A>C		intron_variant	Intron 2 of 14		NM_001386879.1	ENSP00000508235.1

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

African (AFR) AF: 0.0241 AC: 1001 AN: 41510

American (AMR) AF: 0.0825 AC: 1258 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 525 AN: 3464

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5158

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4818

European-Finnish (FIN) AF: 0.100 AC: 1059 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8970 AN: 67936

Other (OTH) AF: 0.103 AC: 216 AN: 2104

Alfa AF: 0.101 Hom.: 121

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
PhyloP100		-2.1
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: rs11045981; hg19: chr12-21486983;