rs143164371

Variant names:

• chr14-24505611-C-A
• rs143164371
• NM_001836.5:c.649G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-24505611-C-A
• chr14-24505611-C-G
• chr14-24505611-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001836.5(CMA1):​c.649G>T​(p.Val217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CMA1 NM_001836.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMA1	NM_001836.5	c.649G>T	p.Val217Leu	missense_variant	Exon 5 of 5	ENST00000250378.7	NP_001827.1
CMA1	NM_001308083.2	c.316G>T	p.Val106Leu	missense_variant	Exon 4 of 4		NP_001295012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMA1	ENST00000250378.7	c.649G>T	p.Val217Leu	missense_variant	Exon 5 of 5	1	NM_001836.5	ENSP00000250378.3
CMA1	ENST00000206446.4	c.316G>T	p.Val106Leu	missense_variant	Exon 4 of 4	1		ENSP00000206446.4
ENSG00000258744	ENST00000555109.1	n.144-2523C>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727076

Gnomad4 AFR exome AF: 0.00

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 Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.
Eigen	Benign	0.034
Eigen_PC	Benign	-0.0041
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.095	T;T
Sift4G	Benign	0.090	T;T
Polyphen		0.97	D;.
Vest4		0.38
MutPred		0.83		Loss of catalytic residue at V217 (P = 0.1314);.;
MVP		0.69
MPC		0.0052
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.57
gMVP		0.62

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

Other links and lift over

dbSNP: rs143164371; hg19: chr14-24974817;