rs8076809

Positions:

• chr17-64103948-A-C
• chr17-64103948-A-G

Variant summary

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

The NM_001433.5(ERN1):​c.55-5707T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,964 control chromosomes in the GnomAD database, including 18,470 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 0.43 (18470 hom., cov: 31)
• Consequence: ERN1 NM_001433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERN1	NM_001433.5	c.55-5707T>G		intron_variant		ENST00000433197.4	NP_001424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERN1	ENST00000433197.4	c.55-5707T>G		intron_variant		1	NM_001433.5	ENSP00000401445	P1
ERN1	ENST00000680433.1	c.55-5707T>G		intron_variant				ENSP00000506094
ERN1	ENST00000680493.1	c.55-5707T>G		intron_variant				ENSP00000505990
ERN1	ENST00000584041.1	n.168-5707T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64740 AN: 151846 Hom.: 18421 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.427 AC: 64846 AN: 151964 Hom.: 18470 Cov.: 31 AF XY: 0.426 AC XY: 31607 AN XY: 74262

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.398

Alfa AF: 0.248 Hom.: 2241

Bravo AF: 0.456

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.57

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: rs8076809; hg19: chr17-62181308;