rs928978

Variant names:

• chr18-908534-A-C
• rs928978
• NM_001099733.2:c.341+171A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-908534-A-C
• chr18-908534-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.341+171A>C		intron_variant	Intron 4 of 4	ENST00000450565.8	NP_001093203.1
ADCYAP1	NM_001117.5	c.341+171A>C		intron_variant	Intron 3 of 3		NP_001108.2
ADCYAP1	XM_005258081.5	c.758+171A>C		intron_variant	Intron 5 of 5		XP_005258138.2
ADCYAP1	XM_047437288.1	c.342-11A>C		intron_variant	Intron 4 of 4		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.341+171A>C		intron_variant	Intron 4 of 4	1	NM_001099733.2	ENSP00000411658.3
ADCYAP1	ENST00000579794.1	c.341+171A>C		intron_variant	Intron 3 of 3	1		ENSP00000462647.1
ADCYAP1	ENST00000269200.5	n.339+171A>C		intron_variant	Intron 2 of 2	2
ADCYAP1	ENST00000581602.1	n.332+171A>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.425 AC: 17600 AN: 41446

American (AMR) AF: 0.629 AC: 9619 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2936 AN: 5136

South Asian (SAS) AF: 0.687 AC: 3313 AN: 4822

European-Finnish (FIN) AF: 0.653 AC: 6904 AN: 10576

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.632 AC: 42945 AN: 67924

Other (OTH) AF: 0.576 AC: 1218 AN: 2114

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
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs928978; hg19: chr18-908535;