chr17-64108404-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERN1	NM_001433.5	MANE Select	c.55-10163G>A		intron	N/A	NP_001424.3	O75460-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERN1	ENST00000433197.4	TSL:1 MANE Select	c.55-10163G>A		intron	N/A	ENSP00000401445.2	O75460-1
	ERN1	ENST00000680433.1		c.55-10163G>A		intron	N/A	ENSP00000506094.1	A0A7P0TAB0
	ERN1	ENST00000680493.1		c.55-10163G>A		intron	N/A	ENSP00000505990.1	A0A7P0TA38

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

African (AFR) AF: 0.878 AC: 36387 AN: 41456

American (AMR) AF: 0.538 AC: 8213 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1635 AN: 3466

East Asian (EAS) AF: 0.442 AC: 2283 AN: 5166

South Asian (SAS) AF: 0.404 AC: 1943 AN: 4812

European-Finnish (FIN) AF: 0.472 AC: 4975 AN: 10532

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25081 AN: 67946

Other (OTH) AF: 0.494 AC: 1041 AN: 2108

Alfa AF: 0.423 Hom.: 28804

Bravo AF: 0.566

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1874087; hg19: chr17-62185764;