chr2-79085584-C-T

Variant names:

• chr2-79085584-C-T
• rs145905447
• NM_006507.4:c.341G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006507.4(REG1B):​c.341G>A​(p.Ser114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: REG1B NM_006507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26227748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1B	NM_006507.4	c.341G>A	p.Ser114Asn	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.341G>A	p.Ser114Asn	missense_variant	Exon 5 of 6	1	NM_006507.4	ENSP00000303206.3
REG1B	ENST00000479258.5	n.1211G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1
REG1B	ENST00000454188.5	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 4	3		ENSP00000387410.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249802 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1460818 Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29 AN XY: 726738

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.0000224 AC: 1 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111510

Other (OTH) AF: 0.0000166 AC: 1 AN: 60330

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341G>A (p.S114N) 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 341, causing the serine (S) at amino acid position 114 to be replaced by an asparagine (N). 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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	.;M
PhyloP100		1.2
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.022	D;D
Sift4G	Uncertain	0.026	D;T
Polyphen		0.28	.;B
Vest4		0.37
MVP		0.22
MPC		0.017
ClinPred		0.69	D
GERP RS		1.1
Varity_R		0.72
gMVP		0.50
Mutation Taster		=98/2	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

dbSNP: rs145905447; hg19: chr2-79312710;