rs377599213

Variant names:

• chr12-51346629-G-GC
• rs377599213
• NM_001971.6:c.9_10insG

Your query was ambiguous. Multiple possible variants found:

• chr12-51346629-G-GC
• chr12-51346629-G-GT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001971.6(CELA1):​c.9_10insG​(p.Leu4AlafsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: CELA1 NM_001971.6 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-51346629-G-GC is Benign according to our data. Variant chr12-51346629-G-GC is described in ClinVar as [Benign]. Clinvar id is 402530.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA1	NM_001971.6	c.9_10insG	p.Leu4AlafsTer21	frameshift_variant	Exon 1 of 8	ENST00000293636.2	NP_001962.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA1	ENST00000293636.2	c.9_10insG	p.Leu4AlafsTer21	frameshift_variant	Exon 1 of 8	1	NM_001971.6	ENSP00000293636.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Common in our data set, gene weakly associated with autoimmune syndrome -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=161/39	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs377599213; hg19: chr12-51740413; COSMIC: COSV53329204; COSMIC: COSV53329204;