12-51346631-A-AAG

Variant names:

• chr12-51346631-A-AAG
• rs370927847
• NM_001971.6:c.7_8insCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001971.6(CELA1):​c.7_8insCT​(p.Val3AlafsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,493,960 control chromosomes in the GnomAD database, including 134,309 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13315 hom., cov: 30)
  • Exomes 𝑓: 0.40 (120994 hom.)
• Consequence: CELA1 NM_001971.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA1	NM_001971.6	MANE Select	c.7_8insCT	p.Val3AlafsTer18	frameshift	Exon 1 of 8	NP_001962.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA1	ENST00000293636.2	TSL:1 MANE Select	c.7_8insCT	p.Val3AlafsTer18	frameshift	Exon 1 of 8	ENSP00000293636.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62623 AN: 151580 Hom.: 13297 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.440

GnomAD2 exomes AF: 0.258 AC: 43271 AN: 167882 AF XY: 0.253

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.397 AC: 532671 AN: 1342264 Hom.: 120994 Cov.: 34 AF XY: 0.395 AC XY: 264564 AN XY: 670590

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.352 AC: 10884 AN: 30884

American (AMR) AF: 0.556 AC: 23365 AN: 42044

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9187 AN: 24742

East Asian (EAS) AF: 0.553 AC: 21100 AN: 38160

South Asian (SAS) AF: 0.303 AC: 24636 AN: 81336

European-Finnish (FIN) AF: 0.348 AC: 17972 AN: 51704

Middle Eastern (MID) AF: 0.386 AC: 2130 AN: 5514

European-Non Finnish (NFE) AF: 0.396 AC: 401146 AN: 1011976

Other (OTH) AF: 0.398 AC: 22251 AN: 55904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.413 AC: 62679 AN: 151696 Hom.: 13315 Cov.: 30 AF XY: 0.415 AC XY: 30753 AN XY: 74110

African (AFR) AF: 0.373 AC: 15445 AN: 41390

American (AMR) AF: 0.516 AC: 7862 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3468

East Asian (EAS) AF: 0.576 AC: 2952 AN: 5126

South Asian (SAS) AF: 0.322 AC: 1543 AN: 4796

European-Finnish (FIN) AF: 0.362 AC: 3797 AN: 10502

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28314 AN: 67876

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.156 Hom.: 794

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=163/37	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs370927847; hg19: chr12-51740415; COSMIC: COSV107306264; COSMIC: COSV107306264;