rs2231187

Variant names:

• chr18-909560-A-G
• rs2231187
• NM_001099733.2:c.456A>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.456A>G​(p.Lys152Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.299 in 1,613,706 control chromosomes in the GnomAD database, including 75,260 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 (5604 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69656 hom.)
• Consequence: ADCYAP1 NM_001099733.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 17 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 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.456A>G	p.Lys152Lys	synonymous	Exon 5 of 5	NP_001093203.1
	ADCYAP1	NM_001117.5		c.456A>G	p.Lys152Lys	synonymous	Exon 4 of 4	NP_001108.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.456A>G	p.Lys152Lys	synonymous	Exon 5 of 5	ENSP00000411658.3
	ADCYAP1	ENST00000579794.1	TSL:1	c.456A>G	p.Lys152Lys	synonymous	Exon 4 of 4	ENSP00000462647.1
	ADCYAP1	ENST00000269200.5	TSL:2	n.454A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38828 AN: 152056 Hom.: 5597 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.281 AC: 70556 AN: 251174 AF XY: 0.276

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.303 AC: 442894 AN: 1461532 Hom.: 69656 Cov.: 37 AF XY: 0.298 AC XY: 216880 AN XY: 727058

African (AFR) AF: 0.106 AC: 3541 AN: 33456

American (AMR) AF: 0.336 AC: 15007 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6437 AN: 26128

East Asian (EAS) AF: 0.229 AC: 9076 AN: 39690

South Asian (SAS) AF: 0.162 AC: 14005 AN: 86226

European-Finnish (FIN) AF: 0.338 AC: 18045 AN: 53398

Middle Eastern (MID) AF: 0.228 AC: 1317 AN: 5764

European-Non Finnish (NFE) AF: 0.322 AC: 358131 AN: 1111780

Other (OTH) AF: 0.287 AC: 17335 AN: 60386

GnomAD4 genome AF: 0.255 AC: 38843 AN: 152174 Hom.: 5604 Cov.: 32 AF XY: 0.252 AC XY: 18716 AN XY: 74382

African (AFR) AF: 0.118 AC: 4894 AN: 41536

American (AMR) AF: 0.301 AC: 4608 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 848 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1199 AN: 5166

South Asian (SAS) AF: 0.161 AC: 775 AN: 4820

European-Finnish (FIN) AF: 0.332 AC: 3515 AN: 10584

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22240 AN: 67992

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.296 Hom.: 17118

Bravo AF: 0.249

Asia WGS AF: 0.169 AC: 590 AN: 3478

EpiCase AF: 0.314

EpiControl AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		4.2
Mutation Taster		=86/14	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: rs2231187; hg19: chr18-909561; COSMIC: COSV52485705; COSMIC: COSV52485705;