Genetic Variant REG1B:p.Ser114Thr (chr2-79085584-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006507.4(REG1B):c.341G>C(p.Ser114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S114N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

REG1B
NM_006507.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28628504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1B	NM_006507.4 link	c.341G>C	p.Ser114Thr	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.341G>C	p.Ser114Thr	missense_variant	Exon 5 of 6	1	NM_006507.4	ENSP00000303206.3	P48304
REG1B	ENST00000479258.5 link	n.1211G>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
REG1B	ENST00000454188.5 link	c.194G>C	p.Ser65Thr	missense_variant	Exon 3 of 4	3		ENSP00000387410.1	H7BZ24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460818

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111510

Other (OTH)

AF:

0.00

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M

PhyloP100

1.2

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.14

Sift

Benign

0.23

T;D

Sift4G

Benign

0.13

T;T

Polyphen

0.90

.;P

Vest4

0.32

MutPred

0.55

.;Loss of catalytic residue at S114 (P = 0.0523);

MVP

0.22

MPC

0.015

ClinPred

0.90

GERP RS

1.1

Varity_R

0.27

gMVP

0.43

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over