Variant chr17-64044120-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001433.5(ERN1):c.2802A>G(p.Thr934=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,609,910 control chromosomes in the GnomAD database, including 433,215 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 0.61 ( 31175 hom., cov: 30)

Exomes 𝑓: 0.74 ( 402040 hom. )

Consequence

ERN1
NM_001433.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.37

Variant links:

Genes affected

ERN1 (HGNC:3449): (endoplasmic reticulum to nucleus signaling 1) This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]

ERN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-4.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERN1	NM_001433.5 linkuse as main transcript	c.2802A>G	p.Thr934=	synonymous_variant	22/22	ENST00000433197.4	NP_001424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERN1	ENST00000433197.4 linkuse as main transcript	c.2802A>G	p.Thr934=	synonymous_variant	22/22	1	NM_001433.5	ENSP00000401445	P1	O75460-1
ERN1	ENST00000680433.1 linkuse as main transcript	c.*1174A>G		3_prime_UTR_variant	20/20			ENSP00000506094
ERN1	ENST00000680625.1 linkuse as main transcript	n.2720A>G		non_coding_transcript_exon_variant	21/21

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

92193

AN:

151798

Hom.:

31174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.616

GnomAD3 exomes

AF:

0.695

AC:

171012

AN:

245926

Hom.:

61476

AF XY:

0.710

AC XY:

94811

AN XY:

133508

show subpopulations

Gnomad AFR exome

AF:

0.277

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.587

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.756

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.761

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.738

AC:

1075712

AN:

1457994

Hom.:

402040

Cov.:

AF XY:

0.741

AC XY:

536961

AN XY:

725032

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.753

Gnomad4 FIN exome

AF:

0.749

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.607

AC:

92217

AN:

151916

Hom.:

31175

Cov.:

AF XY:

0.608

AC XY:

45137

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.617

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.766

Gnomad4 FIN

AF:

0.737

Gnomad4 NFE

AF:

0.760

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.711

Hom.:

53490

Bravo

AF:

0.580

Asia WGS

AF:

0.716

AC:

2488

AN:

3478

EpiCase

AF:

0.747

EpiControl

AF:

0.739

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.046

DANN

Benign

0.59

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over