Genetic Variant NM_015849.3:c.235G>A (chr1-15482272-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015849.3(CELA2B):c.235G>A(p.Gly79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,282 control chromosomes in the GnomAD database, including 58,965 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5882 hom., cov: 32)

Exomes 𝑓: 0.26 ( 53083 hom. )

Consequence

CELA2B
NM_015849.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

28 publications found

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]

CELA2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.6351685E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2B	NM_015849.3 link	c.235G>A	p.Gly79Arg	missense_variant	Exon 4 of 8	ENST00000375910.8	NP_056933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CELA2B	ENST00000375910.8 link	c.235G>A	p.Gly79Arg	missense_variant	Exon 4 of 8	1	NM_015849.3	ENSP00000365075.3
CELA2B	ENST00000422901.1 link	c.292G>A	p.Gly98Arg	missense_variant	Exon 4 of 4	5		ENSP00000399811.1
CELA2B	ENST00000494280.1 link	n.584G>A		non_coding_transcript_exon_variant	Exon 5 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40713

AN:

151818

Hom.:

5876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.281

AC:

70644

AN:

251032

AF XY:

0.271

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.261

AC:

382073

AN:

1461346

Hom.:

53083

Cov.:

AF XY:

0.258

AC XY:

187769

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.256

AC:

8568

AN:

33470

American (AMR)

AF:

0.359

AC:

16035

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4126

AN:

26118

East Asian (EAS)

AF:

0.550

AC:

21805

AN:

39672

South Asian (SAS)

AF:

0.196

AC:

16921

AN:

86242

European-Finnish (FIN)

AF:

0.281

AC:

14992

AN:

53370

Middle Eastern (MID)

AF:

0.150

AC:

862

AN:

5762

European-Non Finnish (NFE)

AF:

0.255

AC:

283072

AN:

1111644

Other (OTH)

AF:

0.260

AC:

15692

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14775

29550

44326

59101

73876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9798

19596

29394

39192

48990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40738

AN:

151936

Hom.:

5882

Cov.:

AF XY:

0.270

AC XY:

20072

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.257

AC:

10654

AN:

41452

American (AMR)

AF:

0.320

AC:

4878

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3468

East Asian (EAS)

AF:

0.559

AC:

2875

AN:

5142

South Asian (SAS)

AF:

0.217

AC:

1049

AN:

4826

European-Finnish (FIN)

AF:

0.281

AC:

2955

AN:

10530

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17110

AN:

67948

Other (OTH)

AF:

0.235

AC:

494

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1505

3010

4516

6021

7526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.257

Hom.:

20720

Bravo

AF:

0.272

TwinsUK

AF:

0.262

AC:

970

ESP6500AA

AF:

0.261

AC:

1149

ESP6500EA

AF:

0.246

AC:

2113

ExAC

AF:

0.277

AC:

33583

Asia WGS

AF:

0.381

AC:

1326

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.090

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.000036

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.28

N;.

PhyloP100

-1.8

PrimateAI

Benign

0.31

PROVEAN

Benign

4.2

N;N

Sift

Benign

0.96

T;T

Sift4G

Benign

0.75

T;T

Vest4

0.051

ClinPred

0.00066

GERP RS

-6.2

Varity_R

0.047

gMVP

0.55

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over