rs2267735

Positions:

• chr7-31095890-C-G

Variant summary

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

The NM_001118.5(ADCYAP1R1):​c.1046+3155C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 619,342 control chromosomes in the GnomAD database, including 80,470 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 (17800 hom., cov: 32)
  • Exomes 𝑓: 0.52 (62670 hom.)
• Consequence: ADCYAP1R1 NM_001118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1R1	NM_001118.5	c.1046+3155C>G		intron_variant		ENST00000304166.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.1046+3155C>G		intron_variant		2	NM_001118.5	A1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72382 AN: 151924 Hom.: 17784 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.516 AC: 240986 AN: 467300 Hom.: 62670 AF XY: 0.516 AC XY: 128339 AN XY: 248588

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.476 AC: 72430 AN: 152042 Hom.: 17800 Cov.: 32 AF XY: 0.475 AC XY: 35298 AN XY: 74302

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.486

Alfa AF: 0.498 Hom.: 2400

Bravo AF: 0.471

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2267735; hg19: chr7-31135504; COSMIC: COSV58443269;