Genetic Variant IAPP:c.80+107A>G (chr12-21373538-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000415.3(IAPP):c.80+107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 787,868 control chromosomes in the GnomAD database, including 22,229 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 0.29 ( 8682 hom., cov: 33)

Exomes 𝑓: 0.19 ( 13547 hom. )

Consequence

IAPP
NM_000415.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.683

Publications

7 publications found

Variant links:

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]

IAPP links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IAPP	NM_000415.3 link	c.80+107A>G		intron_variant	Intron 2 of 2	ENST00000240652.8	NP_000406.1	P10997A0A024RAU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IAPP	ENST00000240652.8 link	c.80+107A>G		intron_variant	Intron 2 of 2	1	NM_000415.3	ENSP00000240652.3		P10997

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44005

AN:

152002

Hom.:

8649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.193

AC:

122393

AN:

635748

Hom.:

13547

Cov.:

AF XY:

0.190

AC XY:

65017

AN XY:

342764

show subpopulations

African (AFR)

AF:

0.576

AC:

9979

AN:

17314

American (AMR)

AF:

0.123

AC:

4719

AN:

38440

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

5207

AN:

20774

East Asian (EAS)

AF:

0.145

AC:

4965

AN:

34218

South Asian (SAS)

AF:

0.161

AC:

10771

AN:

66774

European-Finnish (FIN)

AF:

0.162

AC:

7046

AN:

43534

Middle Eastern (MID)

AF:

0.214

AC:

897

AN:

4200

European-Non Finnish (NFE)

AF:

0.190

AC:

71568

AN:

377256

Other (OTH)

AF:

0.218

AC:

7241

AN:

33238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5384

10769

16153

21538

26922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.290

AC:

44082

AN:

152120

Hom.:

8682

Cov.:

AF XY:

0.282

AC XY:

20933

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.569

AC:

23601

AN:

41478

American (AMR)

AF:

0.182

AC:

2776

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3468

East Asian (EAS)

AF:

0.138

AC:

715

AN:

5178

South Asian (SAS)

AF:

0.166

AC:

802

AN:

4824

European-Finnish (FIN)

AF:

0.145

AC:

1536

AN:

10600

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.189

AC:

12844

AN:

67980

Other (OTH)

AF:

0.268

AC:

566

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1418

2835

4253

5670

7088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.217

Hom.:

3019

Bravo

AF:

0.305

Asia WGS

AF:

0.179

AC:

624

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.75

(source)

DANN

Benign

0.80

PhyloP100

-0.68

PromoterAI

-0.0014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over