rs10165462

chr2-79120477-T-Cchr2-79120477-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000488524.1(REG1A):n.116T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 178,746 control chromosomes in the GnomAD database, including 11,335 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (9428 hom., cov: 32)
  • Exomes 𝑓: 0.36 (1907 hom.)
• Consequence: REG1A ENST00000488524.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

Genes affected

REG1A (HGNC:9951): (regenerating family member 1 alpha) 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 that is secreted by the exocrine pancreas. It is associated with islet cell regeneration and diabetogenesis and may be involved in pancreatic lithogenesis. Reg family members REG1B, 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REG1A	NM_002909.5			upstream_gene_variant		ENST00000233735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REG1A	ENST00000488524.1	n.116T>C		non_coding_transcript_exon_variant	1/3	1
REG1A	ENST00000233735.2			upstream_gene_variant		1	NM_002909.5	P1
REG1A	ENST00000461579.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47227 AN: 151930 Hom.: 9432 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.358 AC: 9547 AN: 26698 Hom.: 1907 Cov.: 0 AF XY: 0.356 AC XY: 4818 AN XY: 13532

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.311 AC: 47213 AN: 152048 Hom.: 9428 Cov.: 32 AF XY: 0.316 AC XY: 23499 AN XY: 74294

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.293

Alfa AF: 0.359 Hom.: 1422

Bravo AF: 0.282

Asia WGS AF: 0.364 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	11
Dann	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs10165462; hg19: chr2-79347603;