12-51346631-A-AAG

Position:

• chr12-51346631-A-AAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001971.6(CELA1):​c.7_8insCT​(p.Val3fs) 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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELA1	NM_001971.6	c.7_8insCT	p.Val3fs	frameshift_variant	1/8	ENST00000293636.2	NP_001962.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELA1	ENST00000293636.2	c.7_8insCT	p.Val3fs	frameshift_variant	1/8	1	NM_001971.6	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

GnomAD3 exomes AF: 0.258 AC: 43271 AN: 167882 Hom.: 12130 AF XY: 0.253 AC XY: 23078 AN XY: 91366

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 SAS exome AF: 0.162

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

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.398

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

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.441

Alfa AF: 0.156 Hom.: 794

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs370927847; hg19: chr12-51740415;