rs758995

Positions:

• chr7-31064948-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.157+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,590,046 control chromosomes in the GnomAD database, including 13,917 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 0.16 (2751 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11166 hom.)
• Consequence: ADCYAP1R1 NM_001118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCYAP1R1	NM_001118.5	c.157+12G>A		intron_variant		ENST00000304166.9	NP_001109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.157+12G>A		intron_variant		2	NM_001118.5	ENSP00000306620	A1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25042 AN: 152080 Hom.: 2736 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.116 AC: 25413 AN: 219266 Hom.: 1920 AF XY: 0.115 AC XY: 13462 AN XY: 117508

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.000418

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.118 AC: 170221 AN: 1437848 Hom.: 11166 Cov.: 28 AF XY: 0.118 AC XY: 84314 AN XY: 713570

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.0748

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.000409

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.165 AC: 25095 AN: 152198 Hom.: 2751 Cov.: 33 AF XY: 0.160 AC XY: 11917 AN XY: 74424

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.156

Alfa AF: 0.144 Hom.: 433

Bravo AF: 0.173

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
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: rs758995; hg19: chr7-31104564; COSMIC: COSV58448438;