18-905124-A-G

Position:

• chr18-905124-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000579794.1(ADCYAP1):​c.-263A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,364,876 control chromosomes in the GnomAD database, including 385,695 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 0.72 (39710 hom., cov: 33)
  • Exomes 𝑓: 0.75 (345985 hom.)
• Consequence: ADCYAP1 ENST00000579794.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.-2+64A>G		intron_variant		ENST00000450565.8	NP_001093203.1
LOC124904340	XR_007066435.1	n.1529T>C		non_coding_transcript_exon_variant	1/2
ADCYAP1	XM_005258081.5	c.416+64A>G		intron_variant			XP_005258138.2
ADCYAP1	XM_047437288.1	c.-2+64A>G		intron_variant			XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.-2+64A>G		intron_variant		1	NM_001099733.2	ENSP00000411658	P1
	ENST00000581719.3	n.1544T>C		non_coding_transcript_exon_variant	1/1
	ENST00000582554.1	n.90+2467T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109252 AN: 151988 Hom.: 39683 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.754 AC: 913975 AN: 1212774 Hom.: 345985 Cov.: 56 AF XY: 0.752 AC XY: 440582 AN XY: 585656

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.905

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.719 AC: 109324 AN: 152102 Hom.: 39710 Cov.: 33 AF XY: 0.720 AC XY: 53531 AN XY: 74386

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.729

Alfa AF: 0.747 Hom.: 42092

Bravo AF: 0.709

Asia WGS AF: 0.802 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.53

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: rs1893154; hg19: chr18-905125;