rs1610037

chr18-910634-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099733.2(ADCYAP1):c.*999A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,168 control chromosomes in the GnomAD database, including 5,806 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 0.26 (5801 hom., cov: 32)
  • Exomes 𝑓: 0.36 (5 hom.)
• Consequence: ADCYAP1 NM_001099733.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.*999A>G		3_prime_UTR_variant	5/5	ENST00000450565.8
ADCYAP1	NM_001117.5	c.*999A>G		3_prime_UTR_variant	4/4
ADCYAP1	XM_005258081.5	c.*999A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.*999A>G		3_prime_UTR_variant	5/5	1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.*999A>G		3_prime_UTR_variant	4/4	1		P1
ADCYAP1	ENST00000581602.1	n.1521A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40010 AN: 152008 Hom.: 5805 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.357 AC: 15 AN: 42 Hom.: 5 Cov.: 0 AF XY: 0.294 AC XY: 10 AN XY: 34

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.263 AC: 40007 AN: 152126 Hom.: 5801 Cov.: 32 AF XY: 0.265 AC XY: 19722 AN XY: 74352

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.267

Alfa AF: 0.312 Hom.: 10772

Bravo AF: 0.252

Asia WGS AF: 0.242 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.1
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1610037; hg19: chr18-910635;