Genetic Variant NM_006507.4:c.217G>C (chr2-79086471-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.217G>C(p.Val73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

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: 0.400

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=0.35885018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1B	NM_006507.4 link	c.217G>C	p.Val73Leu	missense_variant	Exon 4 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.217G>C	p.Val73Leu	missense_variant	Exon 4 of 6	1	NM_006507.4	ENSP00000303206.3	P48304
REG1B	ENST00000476554.1 link	n.629G>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
REG1B	ENST00000479258.5 link	n.324G>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
REG1B	ENST00000454188.5 link	c.70G>C	p.Val24Leu	missense_variant	Exon 2 of 4	3		ENSP00000387410.1	H7BZ24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M

PhyloP100

0.40

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.090

Sift

Benign

0.076

T;D

Sift4G

Uncertain

0.055

T;T

Polyphen

0.72

.;P

Vest4

0.29

MutPred

0.78

.;Gain of sheet (P = 0.1539);

MVP

0.12

MPC

0.012

ClinPred

0.38

GERP RS

2.6

PromoterAI

0.0066

Neutral

(source)

Varity_R

0.19

gMVP

0.67

Mutation Taster

=96/4

polymorphism

(source)

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

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NM_006507.4:c.217G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over