2-79085497-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006507.4(REG1B):c.428G>T(p.Cys143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C143Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

REG1B
NM_006507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.352

Publications

0 publications found

Variant links:

Genes affected

REG1B (HGNC:9952): (regenerating family member 1 beta) This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV based on the primary structures of the encoded proteins. This gene encodes a protein secreted by the exocrine pancreas that is highly similar to the REG1A protein. The related REG1A protein is associated with islet cell regeneration and diabetogenesis, and may be involved in pancreatic lithogenesis. Reg family members REG1A, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication. [provided by RefSeq, Jul 2008]

REG1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046893448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1B	NM_006507.4 link	c.428G>T	p.Cys143Phe	missense_variant	Exon 5 of 6	ENST00000305089.8	NP_006498.1	P48304Q6ICS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
REG1B	ENST00000305089.8 link	c.428G>T	p.Cys143Phe	missense_variant	Exon 5 of 6	1	NM_006507.4	ENSP00000303206.3	P48304
REG1B	ENST00000454188.5 link	c.281G>T	p.Cys94Phe	missense_variant	Exon 3 of 4	3		ENSP00000387410.1	H7BZ24
REG1B	ENST00000479258.5 link	n.*43G>T		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460016

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.000201

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110392

Other (OTH)

AF:

0.0000166

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.428G>T (p.C143F) alteration is located in exon 5 (coding exon 4) of the REG1B gene. This alteration results from a G to T substitution at nucleotide position 428, causing the cysteine (C) at amino acid position 143 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.052

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.24

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

.;N

PhyloP100

-0.35

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.046

Sift

Benign

0.76

T;D

Sift4G

Benign

0.71

T;D

Polyphen

0.019

.;B

Vest4

0.16

MutPred

0.29

.;Gain of glycosylation at S144 (P = 0.0739);

MVP

0.081

MPC

0.010

ClinPred

0.19

GERP RS

0.10

Varity_R

0.23

gMVP

0.52

Mutation Taster

=94/6

polymorphism

(source)

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

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2-79085497-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over