rs8192597

chr18-907674-G-Achr18-907674-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001099733.2(ADCYAP1):c.126G>A(p.Ala42=) 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.126G>A	p.Ala42=	synonymous_variant	3/5	ENST00000450565.8
ADCYAP1	NM_001117.5	c.126G>A	p.Ala42=	synonymous_variant	2/4
ADCYAP1	XM_005258081.5	c.543G>A	p.Ala181=	synonymous_variant	4/6
ADCYAP1	XM_047437288.1	c.126G>A	p.Ala42=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.126G>A	p.Ala42=	synonymous_variant	3/5	1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.126G>A	p.Ala42=	synonymous_variant	2/4	1		P1
	ENST00000582554.1	n.7C>T		non_coding_transcript_exon_variant	1/2	5
ADCYAP1	ENST00000269200.5	n.124G>A		non_coding_transcript_exon_variant	1/3	2

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

GnomAD3 exomes AF: 0.729 AC: 146764 AN: 201196 Hom.: 53919 AF XY: 0.726 AC XY: 81080 AN XY: 111634

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 SAS exome AF: 0.757

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

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.811

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.701

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

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.659

Alfa AF: 0.675 Hom.: 8165

Bravo AF: 0.667

Asia WGS AF: 0.764 AC: 2650 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	15
Dann	Benign	0.90

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

Other links and lift over

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