rs2267734

Positions:

• chr7-31095857-G-A

Variant summary

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

The NM_001118.5(ADCYAP1R1):​c.1046+3122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 646,108 control chromosomes in the GnomAD database, including 88,905 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 0.56 (24363 hom., cov: 32)
  • Exomes 𝑓: 0.51 (64542 hom.)
• Consequence: ADCYAP1R1 NM_001118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1R1	NM_001118.5	c.1046+3122G>A		intron_variant		ENST00000304166.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.1046+3122G>A		intron_variant		2	NM_001118.5	A1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84649 AN: 151828 Hom.: 24334 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.506 AC: 250068 AN: 494162 Hom.: 64542 AF XY: 0.504 AC XY: 132818 AN XY: 263632

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.558 AC: 84730 AN: 151946 Hom.: 24363 Cov.: 32 AF XY: 0.551 AC XY: 40923 AN XY: 74270

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.541

Alfa AF: 0.543 Hom.: 4623

Bravo AF: 0.561

Asia WGS AF: 0.444 AC: 1545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.49

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: rs2267734; hg19: chr7-31135471; COSMIC: COSV58443261;