chr18-907766-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001099733.2(ADCYAP1):c.218C>T(p.Ala73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,469,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ADCYAP1
NM_001099733.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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:

ENSG00000265671 (HGNC:):

ENSG00000265671 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2261177).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2 link	c.218C>T	p.Ala73Val	missense_variant	Exon 3 of 5	ENST00000450565.8	NP_001093203.1	P18509
ADCYAP1	NM_001117.5 link	c.218C>T	p.Ala73Val	missense_variant	Exon 2 of 4		NP_001108.2	P18509
ADCYAP1	XM_005258081.5 link	c.635C>T	p.Ala212Val	missense_variant	Exon 4 of 6		XP_005258138.2	B7Z222
ADCYAP1	XM_047437288.1 link	c.218C>T	p.Ala73Val	missense_variant	Exon 3 of 5		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCYAP1	ENST00000450565.8 link	c.218C>T	p.Ala73Val	missense_variant	Exon 3 of 5	1	NM_001099733.2	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1 link	c.218C>T	p.Ala73Val	missense_variant	Exon 2 of 4	1		ENSP00000462647.1	P18509
ADCYAP1	ENST00000269200.5 link	n.216C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
ENSG00000265671	ENST00000582554.1 link	n.-86G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000689

AC:

AN:

72556

Hom.:

AF XY:

0.0000489

AC XY:

AN XY:

40928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1317116

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

648354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000152

Gnomad4 OTH exome

AF:

0.0000366

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218C>T (p.A73V) alteration is located in exon 3 (coding exon 2) of the ADCYAP1 gene. This alteration results from a C to T substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.43

REVEL

Benign

0.10

Sift4G

Benign

0.29

T;T

Polyphen

0.38

B;B

Vest4

0.20

MutPred

0.30

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.79

MPC

0.58

ClinPred

0.083

GERP RS

4.2

Varity_R

0.071

gMVP

0.33

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over