rs2856966

chr18-907709-A-Gchr18-907709-A-T

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.161A>G	p.Asp54Gly	missense_variant	3/5	ENST00000450565.8
ADCYAP1	NM_001117.5	c.161A>G	p.Asp54Gly	missense_variant	2/4
ADCYAP1	XM_005258081.5	c.578A>G	p.Asp193Gly	missense_variant	4/6
ADCYAP1	XM_047437288.1	c.161A>G	p.Asp54Gly	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.161A>G	p.Asp54Gly	missense_variant	3/5	1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.161A>G	p.Asp54Gly	missense_variant	2/4	1		P1
ADCYAP1	ENST00000269200.5	n.159A>G		non_coding_transcript_exon_variant	1/3	2
	ENST00000582554.1			upstream_gene_variant		5

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

GnomAD3 exomes AF: 0.194 AC: 31734 AN: 163426 Hom.: 3394 AF XY: 0.203 AC XY: 18372 AN XY: 90444

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 SAS exome AF: 0.209

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

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.0584

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.218

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.201

Alfa AF: 0.230 Hom.: 9127

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 v4.3

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;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.76	D
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.48	T
REVEL	Benign	0.17
Sift4G	Benign	0.14	T;T
Polyphen		0.0020	B;B
Vest4		0.10
MPC		0.76
ClinPred		0.013	T
GERP RS		4.0
Varity_R		0.095
gMVP		0.20

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: rs2856966; hg19: chr18-907710; COSMIC: COSV52487380; COSMIC: COSV52487380;