Variant 16-75223157-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001906.6(CTRB1):c.253G>A(p.Val85Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTRB1
NM_001906.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Variant links:

Genes affected

CTRB1 (HGNC:2521): (chymotrypsinogen B1) 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 CTRB1 gene is located head-to-head with the related CTRB2 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 in intron 1 of the CTRB2 gene is diagnostic for this inversion. This CTRB1 gene encodes distinct isoforms, some or all of which may undergo similar processing to generate the mature protein. [provided by RefSeq, Jan 2021]

CTRB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRB1	NM_001906.6 linkuse as main transcript	c.253G>A	p.Val85Met	missense_variant	4/7	ENST00000361017.9	NP_001897.4	P17538
CTRB1	NM_001329190.2 linkuse as main transcript	c.253G>A	p.Val85Met	missense_variant	4/6		NP_001316119.1	P17538

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRB1	ENST00000361017.9 linkuse as main transcript	c.253G>A	p.Val85Met	missense_variant	4/7	1	NM_001906.6	ENSP00000354294.4		P17538
CTRB1	ENST00000495583.1 linkuse as main transcript	c.325G>A	p.Val109Met	missense_variant	3/4	2		ENSP00000463301.1		J3QKZ2

Frequencies

GnomAD3 genomes

AF:

0.0000256

AC:

AN:

117294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000365

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000278

AC:

AN:

970962

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

493024

show subpopulations

Gnomad4 AFR exome

AF:

0.0000389

Gnomad4 AMR exome

AF:

0.0000613

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000318

Gnomad4 OTH exome

AF:

0.0000228

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000256

AC:

AN:

117294

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55492

show subpopulations

Gnomad4 AFR

AF:

0.0000307

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000365

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

Jan 25, 2023

The c.253G>A (p.V85M) alteration is located in exon 4 (coding exon 4) of the CTRB1 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by a methionine (M). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.81

DEOGEN2

Uncertain

0.68

D;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.84

T;T

M_CAP

Pathogenic

0.39

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Uncertain

-0.070

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.5

D;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.024

D;.

Sift4G

Uncertain

0.020

D;D

Polyphen

0.97

D;.

Vest4

0.39

MutPred

0.56

Loss of sheet (P = 0.1158);.;

MVP

0.93

MPC

2.8

ClinPred

0.85

GERP RS

3.2

Varity_R

0.23

gMVP

0.50

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