rs2070707

Positions:

• chr2-79121070-G-T

Variant summary

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

The NM_002909.5(REG1A):​c.64+145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 621,096 control chromosomes in the GnomAD database, including 8,512 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 0.19 (3148 hom., cov: 31)
  • Exomes 𝑓: 0.14 (5364 hom.)
• Consequence: REG1A NM_002909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REG1A	NM_002909.5	c.64+145G>T		intron_variant		ENST00000233735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REG1A	ENST00000233735.2	c.64+145G>T		intron_variant		1	NM_002909.5	P1
REG1A	ENST00000461579.1	n.436+145G>T		intron_variant, non_coding_transcript_variant		1
REG1A	ENST00000488524.1	n.263+145G>T		intron_variant, non_coding_transcript_variant		1
REG1A	ENST00000485184.1	n.91+145G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28013 AN: 150646 Hom.: 3139 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0762

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.139 AC: 65344 AN: 470388 Hom.: 5364 AF XY: 0.139 AC XY: 34170 AN XY: 246012

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0732

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.186 AC: 28048 AN: 150708 Hom.: 3148 Cov.: 31 AF XY: 0.185 AC XY: 13567 AN XY: 73396

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0636

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.190

Alfa AF: 0.163 Hom.: 383

Bravo AF: 0.200

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.35

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: rs2070707; hg19: chr2-79348196; COSMIC: COSV52071155;