Variant rs2856966 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

Variant links:

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]

ADCYAP1 links:

ADCYAP1 (HGNC:):

ADCYAP1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
ADCYAP1	NM_001099733.2 linkuse as main transcript	c.161A>G	p.Asp54Gly	missense_variant	3/5	ENST00000450565.8	NP_001093203.1	P18509
ADCYAP1	NM_001117.5 linkuse as main transcript	c.161A>G	p.Asp54Gly	missense_variant	2/4		NP_001108.2	P18509
ADCYAP1	XM_005258081.5 linkuse as main transcript	c.578A>G	p.Asp193Gly	missense_variant	4/6		XP_005258138.2	B7Z222
ADCYAP1	XM_047437288.1 linkuse as main transcript	c.161A>G	p.Asp54Gly	missense_variant	3/5		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADCYAP1	ENST00000450565.8 linkuse as main transcript	c.161A>G	p.Asp54Gly	missense_variant	3/5	1	NM_001099733.2	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1 linkuse as main transcript	c.161A>G	p.Asp54Gly	missense_variant	2/4	1		ENSP00000462647.1	P18509
ADCYAP1	ENST00000269200.5 linkuse as main transcript	n.159A>G		non_coding_transcript_exon_variant	1/3	2
ENSG00000265671	ENST00000582554.1 linkuse as main transcript	n.-29T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27378

AN:

152002

Hom.:

2859

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.220

AC XY:

152600

AN XY:

695204

show subpopulations

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.:

AF XY:

0.178

AC XY:

13267

AN XY:

74346

show subpopulations

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.69

.;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.48

REVEL

Benign

0.17

Sift4G

Benign

0.14

T;T

Polyphen

0.0020

B;B

Vest4

0.10

MPC

0.76

ClinPred

0.013

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over