NM_001099733.2:c.111-139A>C

Variant names:

• chr18-907520-A-C
• rs8192595
• NM_001099733.2:c.111-139A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099733.2(ADCYAP1):​c.111-139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 765,616 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: ADCYAP1 NM_001099733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

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]

ENSG00000265179 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	NM_001099733.2	MANE Select	c.111-139A>C		intron	N/A	NP_001093203.1
	ADCYAP1	NM_001117.5		c.111-139A>C		intron	N/A	NP_001108.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.111-139A>C		intron	N/A	ENSP00000411658.3
	ADCYAP1	ENST00000579794.1	TSL:1	c.111-139A>C		intron	N/A	ENSP00000462647.1
	ENSG00000265179	ENST00000763713.1		n.224T>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000131 AC: 1 AN: 765616 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 386040

African (AFR) AF: 0.00 AC: 0 AN: 15610

American (AMR) AF: 0.00 AC: 0 AN: 15676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14628

East Asian (EAS) AF: 0.00 AC: 0 AN: 25502

South Asian (SAS) AF: 0.00 AC: 0 AN: 47216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3988

European-Non Finnish (NFE) AF: 0.00000173 AC: 1 AN: 577264

Other (OTH) AF: 0.00 AC: 0 AN: 35512

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.24
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8192595; hg19: chr18-907521;