2-79121665-C-T

Variant names:

• chr2-79121665-C-T
• rs142877017
• NM_002909.5:c.168C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002909.5(REG1A):​c.168C>T​(p.Thr56Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,924 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (17 hom., cov: 32)
  • Exomes 𝑓: 0.014 (182 hom.)
• Consequence: REG1A NM_002909.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.429
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-79121665-C-T is Benign according to our data. Variant chr2-79121665-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1712417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.429 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1773/152262) while in subpopulation NFE AF = 0.0187 (1272/68026). AF 95% confidence interval is 0.0178. There are 17 homozygotes in GnomAd4. There are 800 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002909.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REG1A	NM_002909.5	MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 3 of 6	NP_002900.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REG1A	ENST00000233735.2	TSL:1 MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 3 of 6	ENSP00000233735.1	P05451
	REG1A	ENST00000461579.1	TSL:1	n.540C>T		non_coding_transcript_exon	Exon 2 of 2
	REG1A	ENST00000488524.1	TSL:1	n.367C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1772 AN: 152144 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00280

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00912

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.0128 AC: 3208 AN: 251384 AF XY: 0.0118

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.0275

Gnomad ASJ exome AF: 0.00605

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.0156

Gnomad OTH exome AF: 0.00961

GnomAD4 exome AF: 0.0143 AC: 20845 AN: 1461662 Hom.: 182 Cov.: 31 AF XY: 0.0139 AC XY: 10113 AN XY: 727152

African (AFR) AF: 0.00230 AC: 77 AN: 33474

American (AMR) AF: 0.0267 AC: 1194 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00589 AC: 154 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00883 AC: 762 AN: 86252

European-Finnish (FIN) AF: 0.00356 AC: 190 AN: 53418

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5766

European-Non Finnish (NFE) AF: 0.0159 AC: 17661 AN: 1111818

Other (OTH) AF: 0.0129 AC: 780 AN: 60384

GnomAD4 genome AF: 0.0116 AC: 1773 AN: 152262 Hom.: 17 Cov.: 32 AF XY: 0.0107 AC XY: 800 AN XY: 74450

African (AFR) AF: 0.00279 AC: 116 AN: 41566

American (AMR) AF: 0.0167 AC: 256 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4822

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1272 AN: 68026

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.0153 Hom.: 10

Bravo AF: 0.0125

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0191

EpiControl AF: 0.0129

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Kidney disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142877017; hg19: chr2-79348791;