rs8192595

chr18-907520-A-Gchr18-907520-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.111-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 917,128 control chromosomes in the GnomAD database, including 3,931 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 0.080 (554 hom., cov: 33)
  • Exomes 𝑓: 0.092 (3377 hom.)
• Consequence: ADCYAP1 NM_001099733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.111-139A>G		intron_variant		ENST00000450565.8
ADCYAP1	NM_001117.5	c.111-139A>G		intron_variant
ADCYAP1	XM_005258081.5	c.528-139A>G		intron_variant
ADCYAP1	XM_047437288.1	c.111-139A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.111-139A>G		intron_variant		1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.111-139A>G		intron_variant		1		P1
	ENST00000582554.1	n.90+71T>C		intron_variant, non_coding_transcript_variant		5
ADCYAP1	ENST00000269200.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12216 AN: 152056 Hom.: 553 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.0872

GnomAD4 exome AF: 0.0920 AC: 70413 AN: 764958 Hom.: 3377 Cov.: 10 AF XY: 0.0900 AC XY: 34702 AN XY: 385718

Gnomad4 AFR exome AF: 0.0551

Gnomad4 AMR exome AF: 0.0552

Gnomad4 ASJ exome AF: 0.0631

Gnomad4 EAS exome AF: 0.0691

Gnomad4 SAS exome AF: 0.0408

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0996

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.0803 AC: 12222 AN: 152170 Hom.: 554 Cov.: 33 AF XY: 0.0802 AC XY: 5963 AN XY: 74388

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0711

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0754 Hom.: 242

Bravo AF: 0.0768

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8192595; hg19: chr18-907521;