14-24507429-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001836.5(CMA1):c.136G>C(p.Gly46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,156 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

CMA1
NM_001836.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.250

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063990355).

BP6

Variant 14-24507429-C-G is Benign according to our data. Variant chr14-24507429-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 708801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMA1	NM_001836.5 link	c.136G>C	p.Gly46Arg	missense_variant	Exon 2 of 5	ENST00000250378.7	NP_001827.1	P23946-1Q4FEB3
CMA1	NM_001308083.2 link	c.-125+749G>C		intron_variant	Intron 1 of 3		NP_001295012.1	P23946-2Q4FEB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMA1	ENST00000250378.7 link	c.136G>C	p.Gly46Arg	missense_variant	Exon 2 of 5	1	NM_001836.5	ENSP00000250378.3	P23946-1
CMA1	ENST00000206446.4 link	c.-125+749G>C		intron_variant	Intron 1 of 3	1		ENSP00000206446.4	P23946-2
ENSG00000258744	ENST00000555109.1 link	n.144-705C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

586

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00459

AC:

1154

AN:

251240

Hom.:

AF XY:

0.00478

AC XY:

649

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00844

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00547

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00411

AC:

6006

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3080

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.00849

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00323

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.00399

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00384

AC:

585

AN:

152276

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.00525

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00457

Hom.:

Bravo

AF:

0.00342

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00451

AC:

547

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00649

EpiControl

AF:

0.00765

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.47

M_CAP

Benign

0.077

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.15

Sift

Uncertain

0.022

Sift4G

Benign

0.12

Polyphen

0.96

Vest4

0.28

MVP

0.75

MPC

0.0037

ClinPred

0.069

GERP RS

-1.2

Varity_R

0.45

gMVP

0.66

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