rs2302475

Positions:

• chr7-31081886-T-C

Variant summary

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

The NM_001118.5(ADCYAP1R1):​c.328+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 637,786 control chromosomes in the GnomAD database, including 70,194 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 0.48 (17364 hom., cov: 32)
  • Exomes 𝑓: 0.46 (52830 hom.)
• Consequence: ADCYAP1R1 NM_001118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

Genes affected

ADCYAP1R1 (HGNC:242): (ADCYAP receptor type I) This gene encodes type I adenylate cyclase activating polypeptide receptor, which is a membrane-associated protein and shares significant homology with members of the glucagon/secretin receptor family. This receptor mediates diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2010]

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 (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1R1	NM_001118.5	c.328+132T>C		intron_variant		ENST00000304166.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.328+132T>C		intron_variant		2	NM_001118.5	A1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72198 AN: 151806 Hom.: 17349 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.465 AC: 225804 AN: 485860 Hom.: 52830 AF XY: 0.462 AC XY: 116866 AN XY: 252850

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.475 AC: 72240 AN: 151926 Hom.: 17364 Cov.: 32 AF XY: 0.477 AC XY: 35438 AN XY: 74252

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.448

Alfa AF: 0.463 Hom.: 25673

Bravo AF: 0.478

Asia WGS AF: 0.432 AC: 1504 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	5.7
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2302475; hg19: chr7-31121501; COSMIC: COSV58448737; COSMIC: COSV58448737;