14-24508192-G-C

Variant names:

Variant summary

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

The NM_001308083.2(CMA1):c.-139C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,752 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CMA1
NM_001308083.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.663

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]

CMA1 links:

ENSG00000258744 (HGNC:):

ENSG00000258744 links:

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=0.2518278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMA1	NM_001836.5 link	c.44C>G	p.Ser15Cys	missense_variant	Exon 1 of 5	ENST00000250378.7	NP_001827.1	P23946-1Q4FEB3
CMA1	NM_001308083.2 link	c.-139C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4		NP_001295012.1	P23946-2Q4FEB3
CMA1	NM_001308083.2 link	c.-139C>G		5_prime_UTR_variant	Exon 1 of 4		NP_001295012.1	P23946-2Q4FEB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMA1	ENST00000206446.4 link	c.-139C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1		ENSP00000206446.4	P23946-2
CMA1	ENST00000250378.7 link	c.44C>G	p.Ser15Cys	missense_variant	Exon 1 of 5	1	NM_001836.5	ENSP00000250378.3	P23946-1
CMA1	ENST00000206446.4 link	c.-139C>G		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000206446.4	P23946-2
ENSG00000258744	ENST00000555109.1 link	n.202G>C		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000798

AC:

AN:

250522

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.00000411

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

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:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>G (p.S15C) alteration is located in exon 1 (coding exon 1) of the CMA1 gene. This alteration results from a C to G substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 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

0.074

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.37

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.40

M_CAP

Benign

0.027

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

REVEL

Benign

0.21

Sift

Benign

0.10

Sift4G

Benign

0.076

Polyphen

0.99

Vest4

0.18

MVP

0.83

MPC

0.0030

ClinPred

0.077

GERP RS

4.4

Varity_R

0.12

gMVP

0.71

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