Variant chr7-31064928-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001118.5(ADCYAP1R1):c.149C>T(p.Ser50Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000481 in 1,455,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ADCYAP1R1
NM_001118.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Variant links:

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]

ADCYAP1R1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24032149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCYAP1R1	NM_001118.5 link	c.149C>T	p.Ser50Phe	missense_variant	3/16	ENST00000304166.9	NP_001109.2	P41586-1A0A090N8F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCYAP1R1	ENST00000304166.9 link	c.149C>T	p.Ser50Phe	missense_variant	3/16	2	NM_001118.5	ENSP00000306620.4		P41586-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455646

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.149C>T (p.S50F) alteration is located in exon 3 (coding exon 2) of the ADCYAP1R1 gene. This alteration results from a C to T substitution at nucleotide position 149, causing the serine (S) at amino acid position 50 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;.;.;.;T

Eigen

Benign

-0.076

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D;D;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M;M;.;M;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;.;N;D;N;N

REVEL

Benign

0.13

Sift

Benign

0.053

T;.;D;D;D;D

Sift4G

Uncertain

0.031

D;D;D;D;D;D

Polyphen

0.0060

B;.;.;.;.;B

Vest4

0.53

MutPred

0.34

Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);

MVP

0.74

MPC

1.2

ClinPred

0.94

GERP RS

5.6

Varity_R

0.26

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over