chr1-15467429-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033440.3(CELA2A):​c.683G>A​(p.Arg228Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,988 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.02
Variant links:
Genes affected
CELA2A (HGNC:24609): (chymotrypsin like elastase 2A) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2A is secreted from the pancreas as a zymogen. In other species, elastase 2A has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, May 2009]
CELA2B (HGNC:29995): (chymotrypsin like elastase 2B) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2B is secreted from the pancreas as a zymogen. In other species, elastase 2B has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.054343164).
BP6
Variant 1-15467429-G-A is Benign according to our data. Variant chr1-15467429-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3141913.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 81 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELA2ANM_033440.3 linkuse as main transcriptc.683G>A p.Arg228Gln missense_variant 7/8 ENST00000359621.5
LOC105376767XR_002958256.2 linkuse as main transcriptn.77C>T non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELA2AENST00000359621.5 linkuse as main transcriptc.683G>A p.Arg228Gln missense_variant 7/81 NM_033440.3 P1
CELA2BENST00000494280.1 linkuse as main transcriptn.280G>A non_coding_transcript_exon_variant 2/65

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
80
AN:
152208
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00186
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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
GnomAD3 exomes
AF:
0.000147
AC:
37
AN:
251082
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.00178
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000582
AC:
85
AN:
1461662
Hom.:
1
Cov.:
33
AF XY:
0.0000536
AC XY:
39
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.00146
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000532
AC:
81
AN:
152326
Hom.:
1
Cov.:
31
AF XY:
0.000591
AC XY:
44
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00188
Gnomad4 AMR
AF:
0.000196
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
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.000484
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000189
AC:
23
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
2.9
DANN
Benign
0.79
DEOGEN2
Benign
0.21
T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.0055
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.23
Sift
Benign
0.69
T
Sift4G
Benign
0.67
T
Polyphen
0.0070
B
Vest4
0.061
MVP
0.17
MPC
0.37
ClinPred
0.0099
T
GERP RS
-1.2
Varity_R
0.023
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs139163441; hg19: chr1-15793924; API