17-64039902-C-T

Position:

• chr17-64039902-C-T

Variant summary

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

The NM_001433.5(ERN1):​c.*4086G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,034 control chromosomes in the GnomAD database, including 18,462 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 0.45 (18457 hom., cov: 32)
  • Exomes 𝑓: 0.65 (5 hom.)
• Consequence: ERN1 NM_001433.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERN1	NM_001433.5	c.*4086G>A		3_prime_UTR_variant	22/22	ENST00000433197.4	NP_001424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERN1	ENST00000433197.4	c.*4086G>A		3_prime_UTR_variant	22/22	1	NM_001433.5	ENSP00000401445.2
ERN1	ENST00000680433.1	c.*5392G>A		3_prime_UTR_variant	20/20			ENSP00000506094.1
ERN1	ENST00000680625.1	n.6938G>A		non_coding_transcript_exon_variant	21/21

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68022 AN: 151890 Hom.: 18457 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.654 AC: 17 AN: 26 Hom.: 5 Cov.: 0 AF XY: 0.654 AC XY: 17 AN XY: 26

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.447 AC: 68017 AN: 152008 Hom.: 18457 Cov.: 32 AF XY: 0.444 AC XY: 32986 AN XY: 74290

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.491

Alfa AF: 0.579 Hom.: 38285

Bravo AF: 0.424

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1985961; hg19: chr17-62117262;