12-21359263-T-G

Variant names:

• chr12-21359263-T-G
• rs10841798
• ENST00000307378.10:c.-63+15136A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307378.10(SLCO1A2):​c.-63+15136A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,184 control chromosomes in the GnomAD database, including 1,050 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 0.094 (1050 hom., cov: 32)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 3 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]

IAPP (HGNC:5329): (islet amyloid polypeptide) This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity. [provided by RefSeq, Jul 2016]

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 (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1A2	NM_001386878.1	c.-62-24554A>C		intron_variant	Intron 1 of 14		NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-24559A>C		intron_variant	Intron 3 of 16		NP_001373810.1
SLCO1A2	NM_001386882.2	c.-63+1400A>C		intron_variant	Intron 1 of 14		NP_001373811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-63+15136A>C		intron_variant	Intron 2 of 15	1		ENSP00000305974.6
SLCO1A2	ENST00000453443.5	c.-62-24554A>C		intron_variant	Intron 1 of 4	3		ENSP00000409314.1
SLCO1A2	ENST00000450590.5	c.-57-24559A>C		intron_variant	Intron 1 of 3	4		ENSP00000407462.1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14294 AN: 152066 Hom.: 1052 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0939 AC: 14284 AN: 152184 Hom.: 1050 Cov.: 32 AF XY: 0.102 AC XY: 7586 AN XY: 74388

African (AFR) AF: 0.0571 AC: 2370 AN: 41538

American (AMR) AF: 0.0663 AC: 1014 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2079 AN: 5168

South Asian (SAS) AF: 0.173 AC: 837 AN: 4828

European-Finnish (FIN) AF: 0.208 AC: 2200 AN: 10568

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5416 AN: 68000

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0744 Hom.: 841

Bravo AF: 0.0798

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.84
PhyloP100		0.0060
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: rs10841798; hg19: chr12-21512197;