Genetic Variant ADCYAP1:p.Asn89Asn (chr18-908289-C-T) – ACMG Classification: Benign (-9 pts)

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

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]

ADCYAP1 links:

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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
ADCYAP1	NM_001099733.2 link	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 4 of 5	ENST00000450565.8	NP_001093203.1	P18509
ADCYAP1	NM_001117.5 link	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 3 of 4		NP_001108.2	P18509
ADCYAP1	XM_005258081.5 link	c.684C>T	p.Asn228Asn	synonymous_variant	Exon 5 of 6		XP_005258138.2	B7Z222
ADCYAP1	XM_047437288.1 link	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 4 of 5		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCYAP1	ENST00000450565.8 link	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 4 of 5	1	NM_001099733.2	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1 link	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 3 of 4	1		ENSP00000462647.1	P18509
ADCYAP1	ENST00000269200.5 link	n.265C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2
ADCYAP1	ENST00000581602.1 link	n.258C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152198

Hom.:

Cov.:

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.:

AF XY:

0.000677

AC XY:

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.:

Cov.:

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.:

Cov.:

AF XY:

0.000671

AC XY:

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.:

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over