rs2856966

Variant names:

• chr18-907709-A-G
• rs2856966
• NM_001099733.2:c.161A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-907709-A-G
• chr18-907709-A-T

Variant summary

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

The NM_001099733.2(ADCYAP1):​c.161A>G​(p.Asp54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,555,282 control chromosomes in the GnomAD database, including 37,571 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2858 hom., cov: 33)
  • Exomes 𝑓: 0.22 (34713 hom.)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 29 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 (MetaRNN=0.0048993826).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 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.161A>G	p.Asp54Gly	missense	Exon 3 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.161A>G	p.Asp54Gly	missense	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.161A>G	p.Asp54Gly	missense	Exon 3 of 5	ENSP00000411658.3	P18509
	ADCYAP1	ENST00000579794.1	TSL:1	c.161A>G	p.Asp54Gly	missense	Exon 2 of 4	ENSP00000462647.1	P18509
	ADCYAP1	ENST00000961508.1		c.161A>G	p.Asp54Gly	missense	Exon 2 of 3	ENSP00000631567.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27378 AN: 152002 Hom.: 2859 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.194 AC: 31734 AN: 163426 AF XY: 0.203

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.0555

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.218 AC: 306256 AN: 1403172 Hom.: 34713 Cov.: 60 AF XY: 0.220 AC XY: 152600 AN XY: 695204

African (AFR) AF: 0.104 AC: 3199 AN: 30728

American (AMR) AF: 0.126 AC: 4812 AN: 38052

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8267 AN: 24792

East Asian (EAS) AF: 0.0584 AC: 2149 AN: 36772

South Asian (SAS) AF: 0.214 AC: 17298 AN: 80672

European-Finnish (FIN) AF: 0.175 AC: 6593 AN: 37782

Middle Eastern (MID) AF: 0.320 AC: 1766 AN: 5512

European-Non Finnish (NFE) AF: 0.229 AC: 249451 AN: 1090452

Other (OTH) AF: 0.218 AC: 12721 AN: 58410

GnomAD4 genome AF: 0.180 AC: 27373 AN: 152110 Hom.: 2858 Cov.: 33 AF XY: 0.178 AC XY: 13267 AN XY: 74346

African (AFR) AF: 0.102 AC: 4227 AN: 41512

American (AMR) AF: 0.157 AC: 2398 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3466

East Asian (EAS) AF: 0.0605 AC: 312 AN: 5158

South Asian (SAS) AF: 0.204 AC: 985 AN: 4826

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10602

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15711 AN: 67952

Other (OTH) AF: 0.201 AC: 423 AN: 2108

Alfa AF: 0.224 Hom.: 12063

Bravo AF: 0.175

ESP6500AA AF: 0.0867 AC: 372

ESP6500EA AF: 0.214 AC: 1799

ExAC AF: 0.166 AC: 19049

Asia WGS AF: 0.130 AC: 451 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.35
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Benign	0.48	T
REVEL	Benign	0.17
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.10
MPC		0.76
ClinPred		0.013	T
GERP RS		4.0
Varity_R		0.095
gMVP		0.20
Mutation Taster		=98/2	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: rs2856966; hg19: chr18-907710; COSMIC: COSV52487380; COSMIC: COSV52487380;