Variant rs754716628 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_001836.5(CMA1):c.210G>C(p.Arg70Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CMA1
NM_001836.5 missense, splice_region

Scores

Splicing: ADA: 0.01184

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

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:

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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=0.085935354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMA1	NM_001836.5 link	c.210G>C	p.Arg70Ser	missense_variant, splice_region_variant	Exon 3 of 5	ENST00000250378.7	NP_001827.1	P23946-1Q4FEB3
CMA1	NM_001308083.2 link	c.-124G>C		splice_region_variant	Exon 2 of 4		NP_001295012.1	P23946-2Q4FEB3
CMA1	NM_001308083.2 link	c.-124G>C		5_prime_UTR_variant	Exon 2 of 4		NP_001295012.1	P23946-2Q4FEB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMA1	ENST00000250378.7 link	c.210G>C	p.Arg70Ser	missense_variant, splice_region_variant	Exon 3 of 5	1	NM_001836.5	ENSP00000250378.3	P23946-1
CMA1	ENST00000206446.4 link	c.-124G>C		splice_region_variant	Exon 2 of 4	1		ENSP00000206446.4	P23946-2
CMA1	ENST00000206446.4 link	c.-124G>C		5_prime_UTR_variant	Exon 2 of 4	1		ENSP00000206446.4	P23946-2
ENSG00000258744	ENST00000555109.1 link	n.144-1530C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.19

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.35

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.79

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.055

Vest4

0.15

MutPred

0.49

Loss of methylation at R70 (P = 0.0388);

MVP

0.68

MPC

0.0029

ClinPred

0.057

GERP RS

-9.4

Varity_R

0.56

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over