Variant chr6-169751670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018341.3(ERMARD):c.6+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,554,918 control chromosomes in the GnomAD database, including 16,782 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 0.18 ( 3013 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13769 hom. )

Consequence

ERMARD
NM_018341.3 splice_region, intron

Scores

Splicing: ADA: 0.0001121

Clinical Significance

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

Conservation

PhyloP100: -2.65

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-169751670-C-T is Benign according to our data. Variant chr6-169751670-C-T is described in ClinVar as [Benign]. Clinvar id is 380783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-169751670-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 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.6+7C>T		splice_region_variant, intron_variant		ENST00000366773.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMARD	ENST00000366773.8 linkuse as main transcript	c.6+7C>T		splice_region_variant, intron_variant		2	NM_018341.3	P2	Q5T6L9-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27252

AN:

152124

Hom.:

2994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.0968

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.169

AC:

26920

AN:

159080

Hom.:

2710

AF XY:

0.167

AC XY:

14175

AN XY:

84884

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.131

AC:

183246

AN:

1402674

Hom.:

13769

Cov.:

AF XY:

0.132

AC XY:

91528

AN XY:

692658

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.294

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.179

AC:

27319

AN:

152244

Hom.:

3013

Cov.:

AF XY:

0.179

AC XY:

13313

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.0968

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.100

Hom.:

341

Bravo

AF:

0.191

Asia WGS

AF:

0.294

AC:

1022

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.17

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