chr7-66130777-C-T

Variant summary

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

The NM_014478.5(CRCP):​c.79C>T​(p.Arg27Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,608,554 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CRCP
NM_014478.5 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
Variant links:
Genes affected
CRCP (HGNC:17888): (CGRP receptor component) This gene encodes a membrane protein that functions as part of a receptor complex for a small neuropeptide that increases intracellular cAMP levels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.17230421).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRCPNM_014478.5 linkc.79C>T p.Arg27Cys missense_variant Exon 3 of 6 ENST00000395326.8 NP_055293.1 O75575-1A0A024RDL0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRCPENST00000395326.8 linkc.79C>T p.Arg27Cys missense_variant Exon 3 of 6 1 NM_014478.5 ENSP00000378736.3 O75575-1
ENSG00000249319ENST00000450043.2 linkc.634C>T p.Arg212Cys missense_variant Exon 9 of 12 5 ENSP00000396527.2 H7C0S8

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152048
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250974
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135694
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1456506
Hom.:
0
Cov.:
27
AF XY:
0.00000966
AC XY:
7
AN XY:
724886
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000672
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:
0.00000722
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152048
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.79C>T (p.R27C) alteration is located in exon 3 (coding exon 3) of the CRCP gene. This alteration results from a C to T substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a cysteine (C). 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
0.34
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.5
.;M
PROVEAN
Uncertain
-3.3
.;D
REVEL
Benign
0.17
Sift
Benign
0.070
.;T
Sift4G
Uncertain
0.027
D;T
Polyphen
0.17
.;B
Vest4
0.72
MVP
0.48
MPC
0.60
ClinPred
0.83
D
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.50

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.

Other links and lift over

dbSNP: rs376911180; hg19: chr7-65595764; API