NM_018341.3:c.1234-260A>G

Variant names:

• chr6-169773059-A-G
• rs4145078
• NM_018341.3:c.1234-260A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ERMARD	NM_018341.3	c.1234-260A>G		intron_variant	Intron 12 of 17	ENST00000366773.8	NP_060811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMARD	ENST00000366773.8	c.1234-260A>G		intron_variant	Intron 12 of 17	2	NM_018341.3	ENSP00000355735.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43035 AN: 151310 Hom.: 6762 Cov.: 32

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.: 0 AF XY: 0.235 AC XY: 27128 AN XY: 115654

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.: 32 AF XY: 0.282 AC XY: 20859 AN XY: 73922

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

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs4145078; hg19: chr6-170173155; COSMIC: COSV64647797; COSMIC: COSV64647797;