Genetic Variant NM_015849.3:c.340G>A (chr1-15482377-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.340G>A(p.Asp114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,674 control chromosomes in the GnomAD database, including 57,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.26 ( 5616 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51863 hom. )

Consequence

CELA2B
NM_015849.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Publications

31 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=2.4650486E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2B	NM_015849.3 link	c.340G>A	p.Asp114Asn	missense_variant	Exon 4 of 8	ENST00000375910.8	NP_056933.3	P08218Q6ISP9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CELA2B	ENST00000375910.8 link	c.340G>A	p.Asp114Asn	missense_variant	Exon 4 of 8	1	NM_015849.3	ENSP00000365075.3	P08218
CELA2B	ENST00000494280.1 link	n.689G>A		non_coding_transcript_exon_variant	Exon 5 of 6	5
CELA2B	ENST00000422901.1 link	c.*20G>A		downstream_gene_variant		5		ENSP00000399811.1	Q5JRU4

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39938

AN:

151940

Hom.:

5612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.274

AC:

68796

AN:

251436

AF XY:

0.265

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.259

AC:

378902

AN:

1461616

Hom.:

51863

Cov.:

AF XY:

0.256

AC XY:

186371

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.255

AC:

8544

AN:

33476

American (AMR)

AF:

0.317

AC:

14168

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4119

AN:

26132

East Asian (EAS)

AF:

0.534

AC:

21199

AN:

39690

South Asian (SAS)

AF:

0.195

AC:

16836

AN:

86244

European-Finnish (FIN)

AF:

0.274

AC:

14650

AN:

53380

Middle Eastern (MID)

AF:

0.150

AC:

864

AN:

5766

European-Non Finnish (NFE)

AF:

0.255

AC:

283035

AN:

1111828

Other (OTH)

AF:

0.256

AC:

15487

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

15437

30873

46310

61746

77183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9774

19548

29322

39096

48870

<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:

0.263

AC:

39955

AN:

152058

Hom.:

5616

Cov.:

AF XY:

0.264

AC XY:

19597

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.256

AC:

10603

AN:

41498

American (AMR)

AF:

0.284

AC:

4343

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

550

AN:

3468

East Asian (EAS)

AF:

0.542

AC:

2792

AN:

5152

South Asian (SAS)

AF:

0.216

AC:

1039

AN:

4816

European-Finnish (FIN)

AF:

0.273

AC:

2882

AN:

10552

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17092

AN:

67970

Other (OTH)

AF:

0.230

AC:

486

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1483

2966

4449

5932

7415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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.:

23343

Bravo

AF:

0.265

TwinsUK

AF:

0.262

AC:

970

ALSPAC

AF:

0.250

AC:

965

ESP6500AA

AF:

0.261

AC:

1151

ESP6500EA

AF:

0.245

AC:

2111

ExAC

AF:

0.271

AC:

32906

Asia WGS

AF:

0.361

AC:

1256

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

0.095

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.2

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.12

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00098

LIST_S2

Benign

0.042

MetaRNN

Benign

0.000025

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

PhyloP100

0.10

PrimateAI

Benign

0.29

PROVEAN

Benign

1.2

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.056

MPC

0.30

ClinPred

0.000016

GERP RS

0.47

Varity_R

0.037

gMVP

0.38

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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