Variant 1-236232837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019891.4(ERO1B):c.676G>A(p.Glu226Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,591,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ERO1B
NM_019891.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.486

Variant links:

Genes affected

ERO1B (HGNC:14355): (endoplasmic reticulum oxidoreductase 1 beta) Enables thiol oxidase activity. Involved in protein folding in endoplasmic reticulum. Predicted to be located in membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERO1B links:

LOC124904561 (HGNC:):

LOC124904561 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10455161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERO1B	NM_019891.4 linkuse as main transcript	c.676G>A	p.Glu226Lys	missense_variant, splice_region_variant	9/16	ENST00000354619.10	NP_063944.3
LOC124904561	XR_007066961.1 linkuse as main transcript	n.925-6160C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERO1B	ENST00000354619.10 linkuse as main transcript	c.676G>A	p.Glu226Lys	missense_variant, splice_region_variant	9/16	1	NM_019891.4	ENSP00000346635	P1	Q86YB8-1
ERO1B	ENST00000687487.1 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant, splice_region_variant	9/16			ENSP00000510551

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000459

AC:

AN:

239890

Hom.:

AF XY:

0.0000308

AC XY:

AN XY:

129980

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000299

AC:

AN:

1439826

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

715872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000354

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.676G>A (p.E226K) alteration is located in exon 9 (coding exon 9) of the ERO1B gene. This alteration results from a G to A substitution at nucleotide position 676, causing the glutamic acid (E) at amino acid position 226 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Benign

0.59

DEOGEN2

Benign

0.079

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.82

M_CAP

Benign

0.0063

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.39

MutationTaster

Benign

0.52

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.39

REVEL

Benign

0.069

Sift

Benign

0.82

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.46

MutPred

0.39

Gain of ubiquitination at E226 (P = 0.0054);

MVP

0.33

MPC

0.29

ClinPred

0.067

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over