rs367548577

Variant names:

• chr14-24506194-C-G
• rs367548577
• NM_001836.5:c.434G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-24506194-C-G
• chr14-24506194-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001836.5(CMA1):​c.434G>C​(p.Arg145Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: CMA1 NM_001836.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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]

ENSG00000258744 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMA1	NM_001836.5	c.434G>C	p.Arg145Pro	missense_variant	Exon 4 of 5	ENST00000250378.7	NP_001827.1
CMA1	NM_001308083.2	c.101G>C	p.Arg34Pro	missense_variant	Exon 3 of 4		NP_001295012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMA1	ENST00000250378.7	c.434G>C	p.Arg145Pro	missense_variant	Exon 4 of 5	1	NM_001836.5	ENSP00000250378.3
CMA1	ENST00000206446.4	c.101G>C	p.Arg34Pro	missense_variant	Exon 3 of 4	1		ENSP00000206446.4
ENSG00000258744	ENST00000555109.1	n.144-1940C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

Gnomad4 AFR AF: 0.0000483

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: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;.
Eigen	Benign	0.031
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.85	T;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.30
Sift	Benign	0.17	T;T
Sift4G	Benign	0.17	T;T
Polyphen		1.0	D;.
Vest4		0.50
MutPred		0.69		Loss of MoRF binding (P = 0.0047);.;
MVP		0.80
MPC		0.0074
ClinPred		0.96	D
GERP RS		0.49
Varity_R		0.96
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs367548577; hg19: chr14-24975400;