Variant 16-75204850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001025200.4(CTRB2):c.553G>A(p.Glu185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000065 ( 3 hom. )

Consequence

CTRB2
NM_001025200.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.588

Variant links:

Genes affected

CTRB2 (HGNC:2522): (chymotrypsinogen B2) This gene encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This CTRB2 gene is located head-to-head with the related CTRB1 gene. Some human populations have an alternate haplotype which inverts a 16.6 Kb region containing portions of intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2 genes. In this inversion haplotype exon 1 and flanking sequence is swapped in CTRB1 and CTRB2. This inversion is associated with differential gene expression and increased risk for chronic pancreatitis. The GRCh38 assembly represents the minor allele for SNP rs8048956 of the CTRB1 gene. SNP rs8048956 is diagnostic for this inversion. [provided by RefSeq, Jan 2021]

CTRB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17223108).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRB2	NM_001025200.4 linkuse as main transcript	c.553G>A	p.Glu185Lys	missense_variant	6/7	ENST00000303037.13	NP_001020371.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRB2	ENST00000303037.13 linkuse as main transcript	c.553G>A	p.Glu185Lys	missense_variant	6/7	1	NM_001025200.4	ENSP00000303963	P1

Frequencies

GnomAD3 genomes

AF:

0.0000157

AC:

AN:

127040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000281

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000172

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

135268

Hom.:

AF XY:

0.0000278

AC XY:

AN XY:

71898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000410

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000652

AC:

AN:

1181046

Hom.:

Cov.:

AF XY:

0.0000665

AC XY:

AN XY:

586092

show subpopulations

Gnomad4 AFR exome

AF:

0.0000353

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000215

Gnomad4 NFE exome

AF:

0.0000788

Gnomad4 OTH exome

AF:

0.0000794

GnomAD4 genome

AF:

0.0000157

AC:

AN:

127040

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

60948

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000281

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000172

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.553G>A (p.E185K) alteration is located in exon 6 (coding exon 6) of the CTRB2 gene. This alteration results from a G to A substitution at nucleotide position 553, causing the glutamic acid (E) at amino acid position 185 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.41

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.54

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.3

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.16

MutPred

0.49

Gain of MoRF binding (P = 0.0029);.;.;

MVP

0.47

MPC

0.11

ClinPred

0.071

GERP RS

-0.98

Varity_R

0.11

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over