7-31084818-A-G

Position:

• chr7-31084818-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001118.5(ADCYAP1R1):​c.520A>G​(p.Ile174Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADCYAP1R1 NM_001118.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1R1	NM_001118.5	c.520A>G	p.Ile174Val	missense_variant	8/16	ENST00000304166.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1R1	ENST00000304166.9	c.520A>G	p.Ile174Val	missense_variant	8/16	2	NM_001118.5	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.520A>G (p.I174V) alteration is located in exon 8 (coding exon 7) of the ADCYAP1R1 gene. This alteration results from a A to G substitution at nucleotide position 520, causing the isoleucine (I) at amino acid position 174 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	M;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.84	N;.;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.075	T;.;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.0070	B;.;.;.;B
Vest4		0.56
MutPred		0.74		Gain of methylation at R177 (P = 0.0847);Gain of methylation at R177 (P = 0.0847);.;Gain of methylation at R177 (P = 0.0847);Gain of methylation at R177 (P = 0.0847);
MVP		0.83
MPC		0.30
ClinPred		0.80	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-31124433;