Variant rs4145078 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018341.3(ERMARD):c.1234-260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 377,848 control chromosomes in the GnomAD database, including 13,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6787 hom., cov: 32)

Exomes 𝑓: 0.23 ( 6811 hom. )

Consequence

ERMARD
NM_018341.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

ERMARD (HGNC:21056): (ER membrane associated RNA degradation) The protein encoded by this gene contains 2 transmembrane domains near the C-terminus and is localized in the endoplasmic reticulum. Knockout of this gene in developing rat brain showed that it may be involved in neuronal migration. Mutations in this gene are associated with periventricular nodular heterotopia-6 (PVNH6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

ERMARD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-169773059-A-G is Benign according to our data. Variant chr6-169773059-A-G is described in ClinVar as [Benign]. Clinvar id is 668133.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERMARD	NM_018341.3 linkuse as main transcript	c.1234-260A>G		intron_variant		ENST00000366773.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMARD	ENST00000366773.8 linkuse as main transcript	c.1234-260A>G		intron_variant		2	NM_018341.3	P2	Q5T6L9-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43035

AN:

151310

Hom.:

6762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.235

AC:

53184

AN:

226418

Hom.:

6811

Cov.:

AF XY:

0.235

AC XY:

27128

AN XY:

115654

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.285

AC:

43120

AN:

151430

Hom.:

6787

Cov.:

AF XY:

0.282

AC XY:

20859

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.245

Hom.:

600

Bravo

AF:

0.298

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

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.083

DANN

Benign

0.49

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

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