Variant chr16-75219037-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001906.6(CTRB1):c.30C>G(p.Phe10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,441,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CTRB1
NM_001906.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07319033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRB1	NM_001906.6 linkuse as main transcript	c.30C>G	p.Phe10Leu	missense_variant	1/7	ENST00000361017.9	NP_001897.4	P17538
CTRB1	NM_001329190.2 linkuse as main transcript	c.30C>G	p.Phe10Leu	missense_variant	1/6		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.30C>G	p.Phe10Leu	missense_variant	1/7	1	NM_001906.6	ENSP00000354294.4		P17538

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

217418

Hom.:

AF XY:

0.0000170

AC XY:

AN XY:

117364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000359

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1441650

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

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

May 31, 2023

The c.30C>G (p.F10L) alteration is located in exon 1 (coding exon 1) of the CTRB1 gene. This alteration results from a C to G substitution at nucleotide position 30, causing the phenylalanine (F) at amino acid position 10 to be replaced by a leucine (L). 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

0.35

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.0010

DANN

Benign

0.36

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.20

M_CAP

Benign

0.052

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.69

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.090

REVEL

Benign

0.13

Sift

Benign

0.85

Sift4G

Benign

1.0

Vest4

0.063

MutPred

0.37

Loss of glycosylation at S11 (P = 0.1282);

MVP

0.32

MPC

0.014

ClinPred

0.018

GERP RS

-8.4

Varity_R

0.024

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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