1-21983722-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007352.4(CELA3B):​c.391C>T​(p.Arg131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,614,106 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 11 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 200 hom. )

Consequence

CELA3B
NM_007352.4 missense

Scores

1
10
7

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.359
Variant links:
Genes affected
CELA3B (HGNC:15945): (chymotrypsin like elastase 3B) 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. Unlike other elastases, elastase 3B has little elastolytic activity. Like most of the human elastases, elastase 3B is secreted from the pancreas as a zymogen and, like other serine proteases such as trypsin, chymotrypsin and kallikrein, it has a digestive function in the intestine. Elastase 3B preferentially cleaves proteins after alanine residues. Elastase 3B may also function in the intestinal transport and metabolism of cholesterol. Both elastase 3A and elastase 3B have been referred to as protease E and as elastase 1, and excretion of this protein in fecal material is frequently used as a measure of pancreatic function in clinical assays. [provided by RefSeq, May 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003702402).
BP6
Variant 1-21983722-C-T is Benign according to our data. Variant chr1-21983722-C-T is described in ClinVar as [Benign]. Clinvar id is 719065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELA3BNM_007352.4 linkc.391C>T p.Arg131Cys missense_variant Exon 5 of 8 ENST00000337107.11 NP_031378.1 P08861

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELA3BENST00000337107.11 linkc.391C>T p.Arg131Cys missense_variant Exon 5 of 8 1 NM_007352.4 ENSP00000338369.6 P08861
CELA3BENST00000400277.2 linkc.100C>T p.Arg34Cys missense_variant Exon 2 of 5 5 ENSP00000383135.2 A0A0A0MSA6
CELA3BENST00000374666.1 linkn.442C>T non_coding_transcript_exon_variant Exon 5 of 5 3
ENSG00000285959ENST00000650360.1 linkn.117C>T non_coding_transcript_exon_variant Exon 1 of 9

Frequencies

GnomAD3 genomes
AF:
0.00313
AC:
476
AN:
152154
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00111
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0247
Gnomad SAS
AF:
0.0577
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00884
AC:
2220
AN:
251144
Hom.:
74
AF XY:
0.0111
AC XY:
1507
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.000923
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0245
Gnomad SAS exome
AF:
0.0546
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000405
Gnomad OTH exome
AF:
0.00408
GnomAD4 exome
AF:
0.00423
AC:
6179
AN:
1461834
Hom.:
200
Cov.:
73
AF XY:
0.00577
AC XY:
4194
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.000806
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0204
Gnomad4 SAS exome
AF:
0.0533
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000339
Gnomad4 OTH exome
AF:
0.00551
GnomAD4 genome
AF:
0.00311
AC:
473
AN:
152272
Hom.:
11
Cov.:
32
AF XY:
0.00408
AC XY:
304
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00111
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0247
Gnomad4 SAS
AF:
0.0567
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.000355
Hom.:
0
Bravo
AF:
0.00202
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.000814
AC:
7
ExAC
AF:
0.00957
AC:
1162
EpiCase
AF:
0.000164
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jan 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.42
T;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.063
N
LIST_S2
Uncertain
0.92
D;D
MetaRNN
Benign
0.0037
T;T
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.019
D;D
Sift4G
Uncertain
0.028
D;D
Polyphen
1.0
D;.
Vest4
0.46
MVP
0.40
MPC
0.74
ClinPred
0.049
T
GERP RS
2.4
Varity_R
0.19
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: 5

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: rs149805485; hg19: chr1-22310215; API