18-908534-A-T

Position:

• chr18-908534-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099733.2(ADCYAP1):​c.341+171A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.341+171A>T		intron_variant		ENST00000450565.8	NP_001093203.1
ADCYAP1	NM_001117.5	c.341+171A>T		intron_variant			NP_001108.2
ADCYAP1	XM_005258081.5	c.758+171A>T		intron_variant			XP_005258138.2
ADCYAP1	XM_047437288.1	c.342-11A>T		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>T		intron_variant		1	NM_001099733.2	ENSP00000411658	P1
ADCYAP1	ENST00000579794.1	c.341+171A>T		intron_variant		1		ENSP00000462647	P1
ADCYAP1	ENST00000269200.5	n.339+171A>T		intron_variant, non_coding_transcript_variant		2
ADCYAP1	ENST00000581602.1	n.332+171A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.4
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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;