chr18-906672-C-T

Position:

• chr18-906672-C-T

Variant summary

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

The NM_001099733.2(ADCYAP1):​c.111-987C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,332 control chromosomes in the GnomAD database, including 46,493 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 0.78 (46461 hom., cov: 34)
  • Exomes 𝑓: 0.80 (32 hom.)
• Consequence: ADCYAP1 NM_001099733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.111-987C>T		intron_variant		ENST00000450565.8
LOC124904340	XR_007066435.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.111-987C>T		intron_variant		1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.111-987C>T		intron_variant		1		P1
	ENST00000582554.1	n.90+919G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000581719.3			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118632 AN: 152110 Hom.: 46431 Cov.: 34

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.815

GnomAD4 exome AF: 0.798 AC: 83 AN: 104 Hom.: 32 Cov.: 0 AF XY: 0.813 AC XY: 65 AN XY: 80

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.780 AC: 118720 AN: 152228 Hom.: 46461 Cov.: 34 AF XY: 0.773 AC XY: 57553 AN XY: 74430

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.813

Alfa AF: 0.804 Hom.: 10237

Bravo AF: 0.787

Asia WGS AF: 0.712 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.75

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: rs2846811; hg19: chr18-906673;