1-21981157-C-T

Variant names:

Variant summary

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

The NM_007352.4(CELA3B):c.347C>T(p.Ser116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000732 in 1,611,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 27)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

CELA3B
NM_007352.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.942

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]

CELA3B links:

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=0.07497987).

BP6

Variant 1-21981157-C-T is Benign according to our data. Variant chr1-21981157-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2392829.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA3B	NM_007352.4 link	c.347C>T	p.Ser116Leu	missense_variant	Exon 4 of 8	ENST00000337107.11	NP_031378.1	P08861

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CELA3B	ENST00000337107.11 link	c.347C>T	p.Ser116Leu	missense_variant	Exon 4 of 8	1	NM_007352.4	ENSP00000338369.6	P08861
CELA3B	ENST00000400277.2 link	c.56C>T	p.Ser19Leu	missense_variant	Exon 1 of 5	5		ENSP00000383135.2	A0A0A0MSA6
CELA3B	ENST00000374666.1 link	n.398C>T		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251318

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

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:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000747

AC:

109

AN:

1460016

Hom.:

Cov.:

AF XY:

0.0000840

AC XY:

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000809

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000947

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 28, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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

0.28

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.23

DANN

Benign

0.55

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.072

T;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.46

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0

B;.

Vest4

0.091

MutPred

0.48

Gain of solvent accessibility (P = 0.2384);.;

MVP

0.30

MPC

0.15

ClinPred

0.45

GERP RS

-9.8

Varity_R

0.040

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over