chr1-21980883-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007352.4(CELA3B):​c.189C>T​(p.Ile63Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,612,476 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 10 hom., cov: 29)
Exomes 𝑓: 0.0048 ( 30 hom. )

Consequence

CELA3B
NM_007352.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.30
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 1-21980883-C-T is Benign according to our data. Variant chr1-21980883-C-T is described in ClinVar as [Benign]. Clinvar id is 774391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.3 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELA3BNM_007352.4 linkc.189C>T p.Ile63Ile synonymous_variant Exon 3 of 8 ENST00000337107.11 NP_031378.1 P08861

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELA3BENST00000337107.11 linkc.189C>T p.Ile63Ile synonymous_variant Exon 3 of 8 1 NM_007352.4 ENSP00000338369.6 P08861
CELA3BENST00000374666.1 linkn.240C>T non_coding_transcript_exon_variant Exon 3 of 5 3
CELA3BENST00000400277.2 linkc.-219C>T upstream_gene_variant 5 ENSP00000383135.2 A0A0A0MSA6

Frequencies

GnomAD3 genomes
AF:
0.00509
AC:
769
AN:
151092
Hom.:
10
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00119
Gnomad AMI
AF:
0.0817
Gnomad AMR
AF:
0.00782
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00212
Gnomad FIN
AF:
0.0138
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00511
Gnomad OTH
AF:
0.00930
GnomAD3 exomes
AF:
0.00493
AC:
1237
AN:
250760
Hom.:
7
AF XY:
0.00515
AC XY:
698
AN XY:
135584
show subpopulations
Gnomad AFR exome
AF:
0.000743
Gnomad AMR exome
AF:
0.00532
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00196
Gnomad FIN exome
AF:
0.0134
Gnomad NFE exome
AF:
0.00576
Gnomad OTH exome
AF:
0.00604
GnomAD4 exome
AF:
0.00485
AC:
7084
AN:
1461266
Hom.:
30
Cov.:
56
AF XY:
0.00485
AC XY:
3523
AN XY:
726960
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00541
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00203
Gnomad4 FIN exome
AF:
0.0129
Gnomad4 NFE exome
AF:
0.00512
Gnomad4 OTH exome
AF:
0.00411
GnomAD4 genome
AF:
0.00507
AC:
766
AN:
151210
Hom.:
10
Cov.:
29
AF XY:
0.00542
AC XY:
400
AN XY:
73852
show subpopulations
Gnomad4 AFR
AF:
0.00119
Gnomad4 AMR
AF:
0.00781
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00212
Gnomad4 FIN
AF:
0.0138
Gnomad4 NFE
AF:
0.00511
Gnomad4 OTH
AF:
0.00871
Alfa
AF:
0.00409
Hom.:
0
EpiCase
AF:
0.00654
EpiControl
AF:
0.00640

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
BayesDel_noAF
Benign
-0.77
CADD
Benign
1.7
DANN
Benign
0.80

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: rs143442995; hg19: chr1-22307376; API