1-21983722-C-T

Variant names:

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

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]

CELA3B links:

ENSG00000285959 (HGNC:):

ENSG00000285959 links:

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
CELA3B	NM_007352.4 link	c.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	UniProt
CELA3B	ENST00000337107.11 link	c.391C>T	p.Arg131Cys	missense_variant	Exon 5 of 8	1	NM_007352.4	ENSP00000338369.6	P08861
CELA3B	ENST00000400277.2 link	c.100C>T	p.Arg34Cys	missense_variant	Exon 2 of 5	5		ENSP00000383135.2	A0A0A0MSA6
CELA3B	ENST00000374666.1 link	n.442C>T		non_coding_transcript_exon_variant	Exon 5 of 5	3
ENSG00000285959	ENST00000650360.1 link	n.117C>T		non_coding_transcript_exon_variant	Exon 1 of 9

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152154

Hom.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

Bravo

AF:

0.00202

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000814

AC:

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

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.063

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0037

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.46

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

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.

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