chr1-15476520-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_015849.3(CELA2B):​c.104C>T​(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CELA2B
NM_015849.3 missense

Scores

6
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.213
Variant links:
Genes affected
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21596599).
BP6
Variant 1-15476520-C-T is Benign according to our data. Variant chr1-15476520-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2388139.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELA2BNM_015849.3 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 2/8 ENST00000375910.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELA2BENST00000375910.8 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 2/81 NM_015849.3 P1
CELA2BENST00000422901.1 linkuse as main transcriptc.56C>T p.Ala19Val missense_variant 1/45
CELA2BENST00000494280.1 linkuse as main transcriptn.453C>T non_coding_transcript_exon_variant 3/65

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000596
AC:
15
AN:
251486
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000110
AC:
161
AN:
1461770
Hom.:
0
Cov.:
31
AF XY:
0.0000976
AC XY:
71
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
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:
0.000135
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.0000545
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 GeneticsOct 05, 2021This 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
7.3
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.016
N
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.0
N;N
REVEL
Uncertain
0.45
Sift
Benign
0.16
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.66
P;.
Vest4
0.22
MVP
0.62
MPC
0.34
ClinPred
0.53
D
GERP RS
0.061
Varity_R
0.083
gMVP
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150801399; hg19: chr1-15803015; API