chr2-79085497-C-T

Variant names:

• chr2-79085497-C-T
• NM_006507.4:c.428G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006507.4(REG1B):​c.428G>A​(p.Cys143Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. C143F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: REG1B NM_006507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.352
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0398674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1B	NM_006507.4	c.428G>A	p.Cys143Tyr	missense_variant	Exon 5 of 6	ENST00000305089.8	NP_006498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REG1B	ENST00000305089.8	c.428G>A	p.Cys143Tyr	missense_variant	Exon 5 of 6	1	NM_006507.4	ENSP00000303206.3
REG1B	ENST00000454188.5	c.281G>A	p.Cys94Tyr	missense_variant	Exon 3 of 4	3		ENSP00000387410.1
REG1B	ENST00000479258.5	n.*43G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428G>A (p.C143Y) alteration is located in exon 5 (coding exon 4) of the REG1B gene. This alteration results from a G to A substitution at nucleotide position 428, causing the cysteine (C) at amino acid position 143 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.21
DEOGEN2	Benign	0.051	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.2	.;N
PhyloP100		-0.35
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.043
Sift	Benign	1.0	T;D
Sift4G	Benign	1.0	T;D
Polyphen		0.019	.;B
Vest4		0.16
MutPred		0.31		.;Loss of disorder (P = 0.0978);
MVP		0.081
MPC		0.010
ClinPred		0.14	T
GERP RS		0.10
Varity_R		0.26
gMVP		0.55
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr2-79312623; COSMIC: COSV59307079; COSMIC: COSV59307079;