17-64108404-C-T

Variant names:

• chr17-64108404-C-T
• rs1874087
• NM_001433.5:c.55-10163G>A

Variant summary

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

The NM_001433.5(ERN1):​c.55-10163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,950 control chromosomes in the GnomAD database, including 25,851 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 0.54 (25851 hom., cov: 31)
• Consequence: ERN1 NM_001433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERN1	NM_001433.5	c.55-10163G>A		intron_variant	Intron 1 of 21	ENST00000433197.4	NP_001424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERN1	ENST00000433197.4	c.55-10163G>A		intron_variant	Intron 1 of 21	1	NM_001433.5	ENSP00000401445.2
ERN1	ENST00000680433.1	c.55-10163G>A		intron_variant	Intron 1 of 19			ENSP00000506094.1
ERN1	ENST00000680493.1	c.55-10163G>A		intron_variant	Intron 1 of 1			ENSP00000505990.1
ERN1	ENST00000584041.1	n.168-10163G>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81997 AN: 151830 Hom.: 25782 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.540 AC: 82128 AN: 151950 Hom.: 25851 Cov.: 31 AF XY: 0.544 AC XY: 40394 AN XY: 74276

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.494

Alfa AF: 0.405 Hom.: 18864

Bravo AF: 0.566

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.49

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: rs1874087; hg19: chr17-62185764;