rs758995

Variant names:

• chr7-31064948-G-A
• rs758995
• NM_001118.5:c.157+12G>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.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
• Publications: 5 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ADCYAP1R1	NM_001118.5	c.157+12G>A		intron_variant	Intron 3 of 15	ENST00000304166.9	NP_001109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.157+12G>A		intron_variant	Intron 3 of 15	2	NM_001118.5	ENSP00000306620.4

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

GnomAD2 exomes AF: 0.116 AC: 25413 AN: 219266 AF XY: 0.115

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 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

African (AFR) AF: 0.313 AC: 10324 AN: 32992

American (AMR) AF: 0.0748 AC: 3218 AN: 43022

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3678 AN: 25522

East Asian (EAS) AF: 0.000409 AC: 16 AN: 39086

South Asian (SAS) AF: 0.119 AC: 9830 AN: 82876

European-Finnish (FIN) AF: 0.105 AC: 5460 AN: 52186

Middle Eastern (MID) AF: 0.153 AC: 860 AN: 5638

European-Non Finnish (NFE) AF: 0.118 AC: 129276 AN: 1097080

Other (OTH) AF: 0.127 AC: 7559 AN: 59446

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

African (AFR) AF: 0.308 AC: 12781 AN: 41496

American (AMR) AF: 0.112 AC: 1709 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.116 AC: 559 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1106 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7958 AN: 67994

Other (OTH) AF: 0.156 AC: 329 AN: 2114

Alfa AF: 0.143 Hom.: 685

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
PhyloP100		-0.47
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: rs758995; hg19: chr7-31104564; COSMIC: COSV58448438;