Variant 14-52658016-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014584.3(ERO1A):c.716-7T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,590,650 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 4 hom. )

Consequence

ERO1A
NM_014584.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001055

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0450

Variant links:

Genes affected

ERO1A (HGNC:13280): (endoplasmic reticulum oxidoreductase 1 alpha) Enables oxidoreductase activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ERO1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006106645).

BP6

Variant 14-52658016-A-C is Benign according to our data. Variant chr14-52658016-A-C is described in ClinVar as [Benign]. Clinvar id is 716384.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERO1A	NM_014584.3 linkuse as main transcript	c.716-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000395686.8	NP_055399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERO1A	ENST00000395686.8 linkuse as main transcript	c.716-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014584.3	ENSP00000379042	P1

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

391

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000672

AC:

164

AN:

244064

Hom.:

AF XY:

0.000425

AC XY:

AN XY:

131828

show subpopulations

Gnomad AFR exome

AF:

0.00945

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000711

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.000263

AC:

379

AN:

1438468

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

164

AN XY:

716448

show subpopulations

Gnomad4 AFR exome

AF:

0.00972

Gnomad4 AMR exome

AF:

0.000209

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152182

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00905

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00314

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000840

AC:

102

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0061

MutationTaster

Benign

1.0

Sift4G

Uncertain

0.016

Vest4

0.15

MVP

0.18

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.060

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