rs8192597

Variant names:

• chr18-907674-G-A
• rs8192597
• NM_001099733.2:c.126G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-907674-G-A
• chr18-907674-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001099733.2(ADCYAP1):​c.126G>A​(p.Ala42Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,578,510 control chromosomes in the GnomAD database, including 405,027 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 0.67 (34761 hom., cov: 33)
  • Exomes 𝑓: 0.72 (370266 hom.)
• Consequence: ADCYAP1 NM_001099733.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 13 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.809 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	NM_001099733.2	MANE Select	c.126G>A	p.Ala42Ala	synonymous	Exon 3 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.126G>A	p.Ala42Ala	synonymous	Exon 2 of 4	NP_001108.2	P18509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.126G>A	p.Ala42Ala	synonymous	Exon 3 of 5	ENSP00000411658.3	P18509
	ADCYAP1	ENST00000579794.1	TSL:1	c.126G>A	p.Ala42Ala	synonymous	Exon 2 of 4	ENSP00000462647.1	P18509
	ADCYAP1	ENST00000961508.1		c.126G>A	p.Ala42Ala	synonymous	Exon 2 of 3	ENSP00000631567.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101879 AN: 151958 Hom.: 34741 Cov.: 33

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.658

GnomAD2 exomes AF: 0.729 AC: 146764 AN: 201196 AF XY: 0.726

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.818

Gnomad ASJ exome AF: 0.607

Gnomad EAS exome AF: 0.838

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.719 AC: 1025351 AN: 1426444 Hom.: 370266 Cov.: 62 AF XY: 0.719 AC XY: 509780 AN XY: 708882

African (AFR) AF: 0.522 AC: 16349 AN: 31308

American (AMR) AF: 0.811 AC: 34341 AN: 42326

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 15553 AN: 25328

East Asian (EAS) AF: 0.856 AC: 32359 AN: 37786

South Asian (SAS) AF: 0.751 AC: 62371 AN: 83048

European-Finnish (FIN) AF: 0.714 AC: 27972 AN: 39160

Middle Eastern (MID) AF: 0.604 AC: 3436 AN: 5692

European-Non Finnish (NFE) AF: 0.718 AC: 791354 AN: 1102394

Other (OTH) AF: 0.701 AC: 41616 AN: 59402

GnomAD4 genome AF: 0.670 AC: 101938 AN: 152066 Hom.: 34761 Cov.: 33 AF XY: 0.673 AC XY: 50025 AN XY: 74334

African (AFR) AF: 0.532 AC: 22089 AN: 41488

American (AMR) AF: 0.757 AC: 11583 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2114 AN: 3468

East Asian (EAS) AF: 0.842 AC: 4318 AN: 5126

South Asian (SAS) AF: 0.759 AC: 3659 AN: 4820

European-Finnish (FIN) AF: 0.706 AC: 7471 AN: 10582

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.713 AC: 48441 AN: 67980

Other (OTH) AF: 0.659 AC: 1391 AN: 2110

Alfa AF: 0.688 Hom.: 14460

Bravo AF: 0.667

Asia WGS AF: 0.764 AC: 2650 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8192597; hg19: chr18-907675; COSMIC: COSV52485946; COSMIC: COSV52485946;