Variant rs5248 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001836.5(CMA1):c.210-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,612,974 control chromosomes in the GnomAD database, including 6,185 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 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: 𝑓 0.091 ( 710 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5475 hom. )

Consequence

CMA1
NM_001836.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.7636

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMA1	NM_001836.5 linkuse as main transcript	c.210-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000250378.7	NP_001827.1
CMA1	NM_001308083.2 linkuse as main transcript	c.-124-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001295012.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CMA1	ENST00000250378.7 linkuse as main transcript	c.210-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001836.5	ENSP00000250378	P1	P23946-1
CMA1	ENST00000206446.4 linkuse as main transcript	c.-124-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000206446		P23946-2
	ENST00000555109.1 linkuse as main transcript	n.144-1526T>C	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0908

AC:

13808

AN:

151996

Hom.:

710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0615

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0306

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0759

Gnomad OTH

AF:

0.0932

GnomAD3 exomes

AF:

0.0859

AC:

21490

AN:

250260

Hom.:

1148

AF XY:

0.0857

AC XY:

11593

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0525

Gnomad ASJ exome

AF:

0.0585

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.0765

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0820

AC:

119804

AN:

1460860

Hom.:

5475

Cov.:

AF XY:

0.0822

AC XY:

59762

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0537

Gnomad4 ASJ exome

AF:

0.0604

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.0964

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0785

Gnomad4 OTH exome

AF:

0.0846

GnomAD4 genome

AF:

0.0909

AC:

13832

AN:

152114

Hom.:

710

Cov.:

AF XY:

0.0891

AC XY:

6629

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.0615

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0306

Gnomad4 NFE

AF:

0.0759

Gnomad4 OTH

AF:

0.0927

Alfa

AF:

0.0799

Hom.:

296

Bravo

AF:

0.0960

Asia WGS

AF:

0.155

AC:

537

AN:

3476

EpiCase

AF:

0.0769

EpiControl

AF:

0.0787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.25

SpliceAI score (max)

0.96

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.96

Position offset: -1

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