18-907520-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099733.2(ADCYAP1):​c.111-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 917,128 control chromosomes in the GnomAD database, including 3,931 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 0.080 (554 hom., cov: 33)
  • Exomes 𝑓: 0.092 (3377 hom.)
• Consequence: ADCYAP1 NM_001099733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	NM_001099733.2	MANE Select	c.111-139A>G		intron	N/A	NP_001093203.1
	ADCYAP1	NM_001117.5		c.111-139A>G		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>G		intron	N/A	ENSP00000411658.3
	ADCYAP1	ENST00000579794.1	TSL:1	c.111-139A>G		intron	N/A	ENSP00000462647.1
	ENSG00000265179	ENST00000763713.1		n.224T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12216 AN: 152056 Hom.: 553 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.0872

GnomAD4 exome AF: 0.0920 AC: 70413 AN: 764958 Hom.: 3377 Cov.: 10 AF XY: 0.0900 AC XY: 34702 AN XY: 385718

African (AFR) AF: 0.0551 AC: 860 AN: 15602

American (AMR) AF: 0.0552 AC: 864 AN: 15664

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 923 AN: 14620

East Asian (EAS) AF: 0.0691 AC: 1762 AN: 25502

South Asian (SAS) AF: 0.0408 AC: 1925 AN: 47208

European-Finnish (FIN) AF: 0.110 AC: 3332 AN: 30214

Middle Eastern (MID) AF: 0.0602 AC: 240 AN: 3988

European-Non Finnish (NFE) AF: 0.0996 AC: 57420 AN: 576666

Other (OTH) AF: 0.0870 AC: 3087 AN: 35494

GnomAD4 genome AF: 0.0803 AC: 12222 AN: 152170 Hom.: 554 Cov.: 33 AF XY: 0.0802 AC XY: 5963 AN XY: 74388

African (AFR) AF: 0.0576 AC: 2393 AN: 41514

American (AMR) AF: 0.0711 AC: 1088 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3468

East Asian (EAS) AF: 0.0873 AC: 450 AN: 5152

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4830

European-Finnish (FIN) AF: 0.112 AC: 1190 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6423 AN: 67992

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0780 Hom.: 373

Bravo AF: 0.0768

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.15
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8192595; hg19: chr18-907521;