12-21373949-T-C

Variant names:

• chr12-21373949-T-C
• rs12300126
• NM_000415.3:c.80+518T>C

Variant summary

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

The NM_000415.3(IAPP):​c.80+518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,058 control chromosomes in the GnomAD database, including 5,755 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 0.25 (5755 hom., cov: 33)
• Consequence: IAPP NM_000415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 6 publications found

Genes affected

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]

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000415.3. 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
	IAPP	NM_000415.3	MANE Select	c.80+518T>C		intron	N/A	NP_000406.1
	SLCO1A2	NM_001386878.1		c.-63+29470A>G		intron	N/A	NP_001373807.1
	SLCO1A2	NM_001386881.1		c.-57-39245A>G		intron	N/A	NP_001373810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IAPP	ENST00000240652.8	TSL:1 MANE Select	c.80+518T>C		intron	N/A	ENSP00000240652.3
	SLCO1A2	ENST00000307378.10	TSL:1	c.-63+450A>G		intron	N/A	ENSP00000305974.6
	SLCO1A2	ENST00000453443.5	TSL:3	c.-63+29470A>G		intron	N/A	ENSP00000409314.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38136 AN: 151940 Hom.: 5736 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.251 AC: 38194 AN: 152058 Hom.: 5755 Cov.: 33 AF XY: 0.245 AC XY: 18174 AN XY: 74330

African (AFR) AF: 0.435 AC: 18018 AN: 41458

American (AMR) AF: 0.167 AC: 2553 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3472

East Asian (EAS) AF: 0.138 AC: 715 AN: 5192

South Asian (SAS) AF: 0.167 AC: 805 AN: 4832

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12822 AN: 67936

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.206 Hom.: 5936

Bravo AF: 0.261

Asia WGS AF: 0.167 AC: 582 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.47
PhyloP100		-1.1
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: rs12300126; hg19: chr12-21526883;