Genetic Variant ENST00000579794.1:c.-263A>G (chr18-905124-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 ENST00000579794.1(ADCYAP1):c.-263A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,364,876 control chromosomes in the GnomAD database, including 385,695 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 0.72 ( 39710 hom., cov: 33)

Exomes 𝑓: 0.75 ( 345985 hom. )

Consequence

ADCYAP1
ENST00000579794.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

21 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:

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2 link	c.-2+64A>G		intron_variant	Intron 1 of 4	ENST00000450565.8	NP_001093203.1	P18509

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8 link	c.-2+64A>G		intron_variant	Intron 1 of 4	1	NM_001099733.2	ENSP00000411658.3		P18509

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109252

AN:

151988

Hom.:

39683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.765

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.725

GnomAD4 exome

AF:

0.754

AC:

913975

AN:

1212774

Hom.:

345985

Cov.:

AF XY:

0.752

AC XY:

440582

AN XY:

585656

show subpopulations

African (AFR)

AF:

0.638

AC:

17097

AN:

26786

American (AMR)

AF:

0.630

AC:

12257

AN:

19444

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

11363

AN:

16856

East Asian (EAS)

AF:

0.905

AC:

24881

AN:

27480

South Asian (SAS)

AF:

0.718

AC:

44738

AN:

62290

European-Finnish (FIN)

AF:

0.758

AC:

16459

AN:

21712

Middle Eastern (MID)

AF:

0.702

AC:

3173

AN:

4522

European-Non Finnish (NFE)

AF:

0.759

AC:

747635

AN:

984754

Other (OTH)

AF:

0.743

AC:

36372

AN:

48930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

12241

24483

36724

48966

61207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19778

39556

59334

79112

98890

<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:

0.719

AC:

109324

AN:

152102

Hom.:

39710

Cov.:

AF XY:

0.720

AC XY:

53531

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.641

AC:

26561

AN:

41466

American (AMR)

AF:

0.658

AC:

10066

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

2358

AN:

3472

East Asian (EAS)

AF:

0.916

AC:

4727

AN:

5162

South Asian (SAS)

AF:

0.724

AC:

3486

AN:

4816

European-Finnish (FIN)

AF:

0.760

AC:

8045

AN:

10584

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.759

AC:

51616

AN:

67994

Other (OTH)

AF:

0.729

AC:

1538

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1539

3078

4618

6157

7696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.742

Hom.:

116886

Bravo

AF:

0.709

Asia WGS

AF:

0.802

AC:

2791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.8

(source)

DANN

Benign

0.53

PhyloP100

-0.24

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=299/1

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

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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