18-908289-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001099733.2(ADCYAP1):​c.267C>T​(p.Asn89Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,612,836 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 6 hom. )

Consequence

ADCYAP1
NM_001099733.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 18-908289-C-T is Benign according to our data. Variant chr18-908289-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3834072.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.82 with no splicing effect.
BS2
High AC in GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADCYAP1NM_001099733.2 linkc.267C>T p.Asn89Asn synonymous_variant Exon 4 of 5 ENST00000450565.8 NP_001093203.1 P18509
ADCYAP1NM_001117.5 linkc.267C>T p.Asn89Asn synonymous_variant Exon 3 of 4 NP_001108.2 P18509
ADCYAP1XM_005258081.5 linkc.684C>T p.Asn228Asn synonymous_variant Exon 5 of 6 XP_005258138.2 B7Z222
ADCYAP1XM_047437288.1 linkc.267C>T p.Asn89Asn synonymous_variant Exon 4 of 5 XP_047293244.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADCYAP1ENST00000450565.8 linkc.267C>T p.Asn89Asn synonymous_variant Exon 4 of 5 1 NM_001099733.2 ENSP00000411658.3 P18509
ADCYAP1ENST00000579794.1 linkc.267C>T p.Asn89Asn synonymous_variant Exon 3 of 4 1 ENSP00000462647.1 P18509
ADCYAP1ENST00000269200.5 linkn.265C>T non_coding_transcript_exon_variant Exon 2 of 3 2
ADCYAP1ENST00000581602.1 linkn.258C>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.000848
AC:
129
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.000392
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000743
AC:
184
AN:
247500
Hom.:
0
AF XY:
0.000677
AC XY:
91
AN XY:
134426
show subpopulations
Gnomad AFR exome
AF:
0.000189
Gnomad AMR exome
AF:
0.000586
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.00141
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.00126
AC:
1843
AN:
1460520
Hom.:
6
Cov.:
31
AF XY:
0.00118
AC XY:
854
AN XY:
726556
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000698
Gnomad4 FIN exome
AF:
0.0000943
Gnomad4 NFE exome
AF:
0.00157
Gnomad4 OTH exome
AF:
0.000862
GnomAD4 genome
AF:
0.000847
AC:
129
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.000671
AC XY:
50
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000385
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00108
Hom.:
1
Bravo
AF:
0.00100
EpiCase
AF:
0.00131
EpiControl
AF:
0.00148

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 25, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
12
DANN
Benign
0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149799520; hg19: chr18-908290; API