rs2267735

Variant names:

• chr7-31095890-C-G
• rs2267735
• NM_001118.5:c.1046+3155C>G

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+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
• Publications: 72 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 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+3155C>G		intron	N/A	NP_001109.2
	ADCYAP1R1	NM_001199635.2		c.1046+3155C>G		intron	N/A	NP_001186564.1
	ADCYAP1R1	NM_001199636.2		c.1046+3155C>G		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+3155C>G		intron	N/A	ENSP00000306620.4
	ADCYAP1R1	ENST00000396211.7	TSL:1	c.1046+3155C>G		intron	N/A	ENSP00000379514.2
	ADCYAP1R1	ENST00000409363.5	TSL:1	c.983+3155C>G		intron	N/A	ENSP00000387335.1

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

African (AFR) AF: 0.358 AC: 4646 AN: 12982

American (AMR) AF: 0.475 AC: 10816 AN: 22786

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 7389 AN: 14328

East Asian (EAS) AF: 0.507 AC: 15849 AN: 31234

South Asian (SAS) AF: 0.501 AC: 23741 AN: 47410

European-Finnish (FIN) AF: 0.507 AC: 15847 AN: 31270

Middle Eastern (MID) AF: 0.498 AC: 1026 AN: 2060

European-Non Finnish (NFE) AF: 0.532 AC: 148109 AN: 278552

Other (OTH) AF: 0.508 AC: 13563 AN: 26678

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

African (AFR) AF: 0.363 AC: 15079 AN: 41502

American (AMR) AF: 0.481 AC: 7350 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1793 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2517 AN: 5140

South Asian (SAS) AF: 0.489 AC: 2352 AN: 4808

European-Finnish (FIN) AF: 0.505 AC: 5342 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36375 AN: 67944

Other (OTH) AF: 0.486 AC: 1027 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.77
PhyloP100		0.16
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: rs2267735; hg19: chr7-31135504; COSMIC: COSV58443269;