Genetic Variant NM_001099733.2:c.111-987C>T (chr18-906672-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001099733.2(ADCYAP1):c.111-987C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,332 control chromosomes in the GnomAD database, including 46,493 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 0.78 ( 46461 hom., cov: 34)

Exomes 𝑓: 0.80 ( 32 hom. )

Consequence

ADCYAP1
NM_001099733.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

2 publications found

Variant links:

Genes affected

ADCYAP1 (HGNC:241): (adenylate cyclase activating polypeptide 1) This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

ADCYAP1 links:

ENSG00000265179 (HGNC:):

ENSG00000265179 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099733.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	NM_001099733.2	MANE Select	c.111-987C>T		intron	N/A	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.111-987C>T		intron	N/A	NP_001108.2	P18509

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.111-987C>T	intron	N/A	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1	TSL:1	c.111-987C>T	intron	N/A	ENSP00000462647.1	P18509
ADCYAP1	ENST00000961508.1		c.111-987C>T	intron	N/A	ENSP00000631567.1

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118632

AN:

152110

Hom.:

46431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.883

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.759

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.815

Gnomad OTH

AF:

0.815

GnomAD4 exome

AF:

0.798

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.817

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.780

AC:

118720

AN:

152228

Hom.:

46461

Cov.:

AF XY:

0.773

AC XY:

57553

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.735

AC:

30522

AN:

41550

American (AMR)

AF:

0.817

AC:

12499

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

3063

AN:

3470

East Asian (EAS)

AF:

0.665

AC:

3421

AN:

5144

South Asian (SAS)

AF:

0.759

AC:

3661

AN:

4822

European-Finnish (FIN)

AF:

0.700

AC:

7420

AN:

10604

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.815

AC:

55445

AN:

68020

Other (OTH)

AF:

0.813

AC:

1718

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1372

2745

4117

5490

6862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.787

Hom.:

14379

Bravo

AF:

0.787

Asia WGS

AF:

0.712

AC:

2479

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.75

PhyloP100

-0.066

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over