12-21401804-A-G

Variant names:

• chr12-21401804-A-G
• rs4762822
• NM_001386878.1:c.-63+1615T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386878.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	NM_001386878.1		c.-63+1615T>C		intron	N/A	NP_001373807.1
	SLCO1A2	NM_001386881.1		c.-58+16078T>C		intron	N/A	NP_001373810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	ENST00000453443.5	TSL:3	c.-63+1615T>C		intron	N/A	ENSP00000409314.1
	SLCO1A2	ENST00000450590.5	TSL:4	c.-58+1615T>C		intron	N/A	ENSP00000407462.1
	SLCO1A2	ENST00000435179.5	TSL:4	c.-58+16078T>C		intron	N/A	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

African (AFR) AF: 0.370 AC: 15315 AN: 41372

American (AMR) AF: 0.447 AC: 6807 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5162

South Asian (SAS) AF: 0.399 AC: 1924 AN: 4820

European-Finnish (FIN) AF: 0.390 AC: 4046 AN: 10376

Middle Eastern (MID) AF: 0.528 AC: 150 AN: 284

European-Non Finnish (NFE) AF: 0.474 AC: 32099 AN: 67724

Other (OTH) AF: 0.439 AC: 918 AN: 2090

Alfa AF: 0.455 Hom.: 10140

Bravo AF: 0.431

Asia WGS AF: 0.355 AC: 1208 AN: 3398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		0.019

Splicing

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

Other links and lift over

dbSNP: rs4762822; hg19: chr12-21554738;