Variant chr2-79121665-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.429

Variant links:

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]

REG1A links:

REG1A (HGNC:):

REG1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG1A	NM_002909.5 linkuse as main transcript	c.168C>T	p.Thr56Thr	synonymous_variant	3/6	ENST00000233735.2	NP_002900.2	P05451A8K7G6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
REG1A	ENST00000233735.2 linkuse as main transcript	c.168C>T	p.Thr56Thr	synonymous_variant	3/6	1	NM_002909.5	ENSP00000233735.1	P05451
REG1A	ENST00000461579.1 linkuse as main transcript	n.540C>T		non_coding_transcript_exon_variant	2/2	1
REG1A	ENST00000488524.1 linkuse as main transcript	n.367C>T		non_coding_transcript_exon_variant	3/3	1
REG1A	ENST00000485184.1 linkuse as main transcript	n.195C>T		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1772

AN:

152144

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0128

AC:

3208

AN:

251384

Hom.:

AF XY:

0.0118

AC XY:

1608

AN XY:

135864

show subpopulations

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 SAS exome

AF:

0.00781

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.:

AF XY:

0.0139

AC XY:

10113

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.00589

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00883

Gnomad4 FIN exome

AF:

0.00356

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0116

AC:

1773

AN:

152262

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

800

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00933

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.0187

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0191

EpiControl

AF:

0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Kidney disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.5

DANN

Benign

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over