NM_001836.5:c.470C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001836.5(CMA1):​c.470C>A​(p.Pro157Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CMA1
NM_001836.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.218
Variant links:
Genes affected
CMA1 (HGNC:2097): (chymase 1) This gene encodes a chymotryptic serine proteinase that belongs to the peptidase family S1. It is expressed in mast cells and is thought to function in the degradation of the extracellular matrix, the regulation of submucosal gland secretion, and the generation of vasoactive peptides. In the heart and blood vessels, this protein, rather than angiotensin converting enzyme, is largely responsible for converting angiotensin I to the vasoactive peptide angiotensin II. Alternative splicing results in multiple variants. [provided by RefSeq, Apr 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03669378).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CMA1NM_001836.5 linkc.470C>A p.Pro157Gln missense_variant Exon 4 of 5 ENST00000250378.7 NP_001827.1 P23946-1Q4FEB3
CMA1NM_001308083.2 linkc.137C>A p.Pro46Gln missense_variant Exon 3 of 4 NP_001295012.1 P23946-2Q4FEB3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CMA1ENST00000250378.7 linkc.470C>A p.Pro157Gln missense_variant Exon 4 of 5 1 NM_001836.5 ENSP00000250378.3 P23946-1
CMA1ENST00000206446.4 linkc.137C>A p.Pro46Gln missense_variant Exon 3 of 4 1 ENSP00000206446.4 P23946-2
ENSG00000258744ENST00000555109.1 linkn.144-1976G>T intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
250870
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135560
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152278
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000770
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000272
Hom.:
0
Bravo
AF:
0.000227
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000988
AC:
12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
13
DANN
Benign
0.93
DEOGEN2
Uncertain
0.47
T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.14
T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.084
Sift
Benign
0.26
T;T
Sift4G
Benign
0.22
T;T
Polyphen
0.74
P;.
Vest4
0.17
MVP
0.78
MPC
0.0076
ClinPred
0.13
T
GERP RS
2.5
Varity_R
0.18
gMVP
0.55

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: rs139700002; hg19: chr14-24975364; API