12-21401804-A-G

Position:

• chr12-21401804-A-G

Variant summary

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

The NM_001386878.1(SLCO1A2):​c.-63+1615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,420 control chromosomes in the GnomAD database, including 14,064 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 0.43 (14064 hom., cov: 32)
• Consequence: SLCO1A2 NM_001386878.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

SLCO1A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1A2	NM_001386878.1	c.-63+1615T>C		intron_variant			NP_001373807.1
SLCO1A2	NM_001386881.1	c.-58+16078T>C		intron_variant			NP_001373810.1
SLCO1A2	XM_011520819.2	c.-58+1615T>C		intron_variant			XP_011519121.1
SLCO1A2	XM_024449138.2	c.-190+1615T>C		intron_variant			XP_024304906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000453443.5	c.-63+1615T>C		intron_variant		3		ENSP00000409314.1
SLCO1A2	ENST00000450590.5	c.-58+1615T>C		intron_variant		4		ENSP00000407462.1
SLCO1A2	ENST00000435179.5	c.-58+16078T>C		intron_variant		4		ENSP00000401195.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64893 AN: 151304 Hom.: 14064 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.429 AC: 64920 AN: 151420 Hom.: 14064 Cov.: 32 AF XY: 0.425 AC XY: 31474 AN XY: 73976

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.439

Alfa AF: 0.454 Hom.: 8751

Bravo AF: 0.431

Asia WGS AF: 0.355 AC: 1208 AN: 3398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4762822; hg19: chr12-21554738;