Genetic Variant CELA1:p.Leu4ThrfsTer21 (chr12-51346629-G-GT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001971.6(CELA1):c.9_10insA(p.Leu4ThrfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,475,946 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CELA1
NM_001971.6 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

3 publications found

Variant links:

Genes affected

CELA1 (HGNC:3308): (chymotrypsin like elastase 1) 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, pancreatic elastase 1 is not expressed in the pancreas. To date, elastase 1 expression has only been detected in skin keratinocytes. Clinical literature that describes human elastase 1 activity in the pancreas or fecal material is actually referring to chymotrypsin-like elastase family, member 3B. [provided by RefSeq, May 2009]

CELA1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001971.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001971.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA1	NM_001971.6	MANE Select	c.9_10insA	p.Leu4ThrfsTer21	frameshift	Exon 1 of 8	NP_001962.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA1	ENST00000293636.2	TSL:1 MANE Select	c.9_10insA	p.Leu4ThrfsTer21	frameshift	Exon 1 of 8	ENSP00000293636.1	Q9UNI1

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

53088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000616

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:

0.000215

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000751

AC:

AN:

133074

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000719

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000169

AC:

AN:

1422816

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

709764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32736

American (AMR)

AF:

0.0000231

AC:

AN:

43298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25792

East Asian (EAS)

AF:

0.00

AC:

AN:

39076

South Asian (SAS)

AF:

0.00

AC:

AN:

85510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000204

AC:

AN:

1078650

Other (OTH)

AF:

0.0000170

AC:

AN:

58894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000113

AC:

AN:

53130

Hom.:

Cov.:

AF XY:

0.0000388

AC XY:

AN XY:

25802

show subpopulations

African (AFR)

AF:

0.0000615

AC:

AN:

16262

American (AMR)

AF:

0.00

AC:

AN:

3688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1352

East Asian (EAS)

AF:

0.00

AC:

AN:

984

South Asian (SAS)

AF:

0.00

AC:

AN:

2226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.000215

AC:

AN:

23206

Other (OTH)

AF:

0.00

AC:

AN:

668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=163/37

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over