Variant 1-236218524-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_019891.4(ERO1B):c.1396A>G(p.Ser466Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,438,170 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

ERO1B
NM_019891.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.78

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:

ERO1B (HGNC:):

ERO1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-236218524-T-C is Benign according to our data. Variant chr1-236218524-T-C is described in ClinVar as [Benign]. Clinvar id is 777106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (820/152186) while in subpopulation AFR AF= 0.0175 (726/41566). AF 95% confidence interval is 0.0164. There are 11 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERO1B	NM_019891.4 linkuse as main transcript	c.1396A>G	p.Ser466Gly	missense_variant	16/16	ENST00000354619.10	NP_063944.3	Q86YB8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERO1B	ENST00000354619.10 linkuse as main transcript	c.1396A>G	p.Ser466Gly	missense_variant	16/16	1	NM_019891.4	ENSP00000346635.5		Q86YB8-1

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

816

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00151

AC:

276

AN:

183206

Hom.:

AF XY:

0.00112

AC XY:

114

AN XY:

101488

show subpopulations

Gnomad AFR exome

AF:

0.0185

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000489

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.000766

GnomAD4 exome

AF:

0.000576

AC:

741

AN:

1285984

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

326

AN XY:

632160

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000169

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00539

AC:

820

AN:

152186

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00643

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00178

AC:

216

Asia WGS

AF:

0.00145

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.14

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.87

REVEL

Benign

0.035

Sift

Benign

0.23

Sift4G

Benign

0.33

Polyphen

0.020

Vest4

0.12

MVP

0.44

MPC

0.24

ClinPred

0.014

GERP RS

5.5

Varity_R

0.082

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.67

Position offset: 0

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