chr1-21980883-C-T

Variant names:

• chr1-21980883-C-T
• rs143442995
• NM_007352.4:c.189C>T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_007352.4(CELA3B):​c.189C>T​(p.Ile63Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,612,476 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (10 hom., cov: 29)
  • Exomes 𝑓: 0.0048 (30 hom.)
• Consequence: CELA3B NM_007352.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

Genes affected

CELA3B (HGNC:15945): (chymotrypsin like elastase 3B) 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, elastase 3B has little elastolytic activity. Like most of the human elastases, elastase 3B is secreted from the pancreas as a zymogen and, like other serine proteases such as trypsin, chymotrypsin and kallikrein, it has a digestive function in the intestine. Elastase 3B preferentially cleaves proteins after alanine residues. Elastase 3B may also function in the intestinal transport and metabolism of cholesterol. Both elastase 3A and elastase 3B have been referred to as protease E and as elastase 1, and excretion of this protein in fecal material is frequently used as a measure of pancreatic function in clinical assays. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-21980883-C-T is Benign according to our data. Variant chr1-21980883-C-T is described in ClinVar as [Benign]. Clinvar id is 774391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.3 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA3B	NM_007352.4	c.189C>T	p.Ile63Ile	synonymous_variant	Exon 3 of 8	ENST00000337107.11	NP_031378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA3B	ENST00000337107.11	c.189C>T	p.Ile63Ile	synonymous_variant	Exon 3 of 8	1	NM_007352.4	ENSP00000338369.6
CELA3B	ENST00000374666.1	n.240C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3
CELA3B	ENST00000400277.2	c.-219C>T		upstream_gene_variant		5		ENSP00000383135.2

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 769 AN: 151092 Hom.: 10 Cov.: 29

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.0817

Gnomad AMR AF: 0.00782

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00212

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00511

Gnomad OTH AF: 0.00930

GnomAD3 exomes AF: 0.00493 AC: 1237 AN: 250760 Hom.: 7 AF XY: 0.00515 AC XY: 698 AN XY: 135584

Gnomad AFR exome AF: 0.000743

Gnomad AMR exome AF: 0.00532

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00196

Gnomad FIN exome AF: 0.0134

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00485 AC: 7084 AN: 1461266 Hom.: 30 Cov.: 56 AF XY: 0.00485 AC XY: 3523 AN XY: 726960

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.00512

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.00507 AC: 766 AN: 151210 Hom.: 10 Cov.: 29 AF XY: 0.00542 AC XY: 400 AN XY: 73852

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.00781

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00212

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00511

Gnomad4 OTH AF: 0.00871

Alfa AF: 0.00409 Hom.: 0

EpiCase AF: 0.00654

EpiControl AF: 0.00640

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs143442995; hg19: chr1-22307376;