rs41275208

Positions:

• chr12-21373509-C-A

Variant summary

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

The NM_000415.3(IAPP):​c.80+78C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 947,318 control chromosomes in the GnomAD database, including 996 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 0.044 (160 hom., cov: 33)
  • Exomes 𝑓: 0.042 (836 hom.)
• Consequence: IAPP NM_000415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IAPP	NM_000415.3	c.80+78C>A		intron_variant		ENST00000240652.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IAPP	ENST00000240652.8	c.80+78C>A		intron_variant		1	NM_000415.3	P1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6737 AN: 152122 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0569

GnomAD4 exome AF: 0.0424 AC: 33686 AN: 795078 Hom.: 836 Cov.: 10 AF XY: 0.0427 AC XY: 17996 AN XY: 421376

Gnomad4 AFR exome AF: 0.0573

Gnomad4 AMR exome AF: 0.0325

Gnomad4 ASJ exome AF: 0.0576

Gnomad4 EAS exome AF: 0.0000549

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0340

Gnomad4 NFE exome AF: 0.0452

Gnomad4 OTH exome AF: 0.0454

GnomAD4 genome AF: 0.0443 AC: 6743 AN: 152240 Hom.: 160 Cov.: 33 AF XY: 0.0427 AC XY: 3180 AN XY: 74424

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0443

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.00988 Hom.: 5

Bravo AF: 0.0455

Asia WGS AF: 0.0180 AC: 64 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41275208; hg19: chr12-21526443;