rs2267734

Variant names:

• chr7-31095857-G-A
• rs2267734
• NM_001118.5:c.1046+3122G>A

Variant summary

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

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001118.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1R1	NM_001118.5	MANE Select	c.1046+3122G>A		intron	N/A	NP_001109.2
	ADCYAP1R1	NM_001199635.2		c.1046+3122G>A		intron	N/A	NP_001186564.1
	ADCYAP1R1	NM_001199636.2		c.1046+3122G>A		intron	N/A	NP_001186565.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1R1	ENST00000304166.9	TSL:2 MANE Select	c.1046+3122G>A		intron	N/A	ENSP00000306620.4
	ADCYAP1R1	ENST00000396211.7	TSL:1	c.1046+3122G>A		intron	N/A	ENSP00000379514.2
	ADCYAP1R1	ENST00000409363.5	TSL:1	c.983+3122G>A		intron	N/A	ENSP00000387335.1

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

African (AFR) AF: 0.688 AC: 9500 AN: 13800

American (AMR) AF: 0.375 AC: 10216 AN: 27240

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 7801 AN: 15808

East Asian (EAS) AF: 0.410 AC: 12876 AN: 31420

South Asian (SAS) AF: 0.461 AC: 23780 AN: 51600

European-Finnish (FIN) AF: 0.503 AC: 18260 AN: 36322

Middle Eastern (MID) AF: 0.503 AC: 1179 AN: 2342

European-Non Finnish (NFE) AF: 0.528 AC: 152098 AN: 287896

Other (OTH) AF: 0.518 AC: 14358 AN: 27734

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

African (AFR) AF: 0.692 AC: 28658 AN: 41432

American (AMR) AF: 0.453 AC: 6923 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.388 AC: 1987 AN: 5122

South Asian (SAS) AF: 0.457 AC: 2197 AN: 4804

European-Finnish (FIN) AF: 0.500 AC: 5285 AN: 10578

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36240 AN: 67944

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.49
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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