chr18-908534-A-C

Position:

• chr18-908534-A-C

Variant summary

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

The NM_001099733.2(ADCYAP1):​c.341+171A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,976 control chromosomes in the GnomAD database, including 25,734 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 0.57 (25734 hom., cov: 32)
• Consequence: ADCYAP1 NM_001099733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.341+171A>C		intron_variant		ENST00000450565.8	NP_001093203.1
ADCYAP1	NM_001117.5	c.341+171A>C		intron_variant			NP_001108.2
ADCYAP1	XM_005258081.5	c.758+171A>C		intron_variant			XP_005258138.2
ADCYAP1	XM_047437288.1	c.342-11A>C		splice_polypyrimidine_tract_variant, intron_variant			XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.341+171A>C		intron_variant		1	NM_001099733.2	ENSP00000411658	P1
ADCYAP1	ENST00000579794.1	c.341+171A>C		intron_variant		1		ENSP00000462647	P1
ADCYAP1	ENST00000269200.5	n.339+171A>C		intron_variant, non_coding_transcript_variant		2
ADCYAP1	ENST00000581602.1	n.332+171A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87126 AN: 151856 Hom.: 25721 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.570

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87159 AN: 151976 Hom.: 25734 Cov.: 32 AF XY: 0.577 AC XY: 42838 AN XY: 74286

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.576

Alfa AF: 0.608 Hom.: 4424

Bravo AF: 0.561

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.4
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs928978; hg19: chr18-908535;