chr1-21980883-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007352.4. 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
	CELA3B	NM_007352.4	MANE Select	c.189C>T	p.Ile63Ile	synonymous	Exon 3 of 8	NP_031378.1	P08861

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA3B	ENST00000337107.11	TSL:1 MANE Select	c.189C>T	p.Ile63Ile	synonymous	Exon 3 of 8	ENSP00000338369.6	P08861
	CELA3B	ENST00000374666.1	TSL:3	n.240C>T		non_coding_transcript_exon	Exon 3 of 5
	CELA3B	ENST00000400277.2	TSL:5	c.-219C>T		upstream_gene	N/A	ENSP00000383135.2	A0A0A0MSA6

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

GnomAD2 exomes AF: 0.00493 AC: 1237 AN: 250760 AF XY: 0.00515

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 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

African (AFR) AF: 0.000538 AC: 18 AN: 33468

American (AMR) AF: 0.00541 AC: 242 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00203 AC: 175 AN: 86230

European-Finnish (FIN) AF: 0.0129 AC: 686 AN: 53368

Middle Eastern (MID) AF: 0.00282 AC: 16 AN: 5668

European-Non Finnish (NFE) AF: 0.00512 AC: 5694 AN: 1111634

Other (OTH) AF: 0.00411 AC: 248 AN: 60362

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

African (AFR) AF: 0.00119 AC: 49 AN: 41320

American (AMR) AF: 0.00781 AC: 118 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00212 AC: 10 AN: 4710

European-Finnish (FIN) AF: 0.0138 AC: 145 AN: 10478

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00511 AC: 346 AN: 67742

Other (OTH) AF: 0.00871 AC: 18 AN: 2066

Alfa AF: 0.00409 Hom.: 0

EpiCase AF: 0.00654

EpiControl AF: 0.00640

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.80
PhyloP100		-2.3
PromoterAI		-0.042	Neutral
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs143442995; hg19: chr1-22307376;