chr6-169773059-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• periventricular nodular heterotopia 6

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

African (AFR) AF: 0.407 AC: 2819 AN: 6934

American (AMR) AF: 0.279 AC: 2288 AN: 8214

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 2288 AN: 8580

East Asian (EAS) AF: 0.326 AC: 6598 AN: 20236

South Asian (SAS) AF: 0.260 AC: 1126 AN: 4330

European-Finnish (FIN) AF: 0.168 AC: 2762 AN: 16416

Middle Eastern (MID) AF: 0.220 AC: 259 AN: 1178

European-Non Finnish (NFE) AF: 0.216 AC: 31420 AN: 145666

Other (OTH) AF: 0.244 AC: 3624 AN: 14864

GnomAD4 genome AF: 0.285 AC: 43120 AN: 151430 Hom.: 6787 Cov.: 32 AF XY: 0.282 AC XY: 20859 AN XY: 73922

African (AFR) AF: 0.419 AC: 17312 AN: 41282

American (AMR) AF: 0.268 AC: 4076 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3464

East Asian (EAS) AF: 0.328 AC: 1683 AN: 5138

South Asian (SAS) AF: 0.297 AC: 1421 AN: 4790

European-Finnish (FIN) AF: 0.162 AC: 1681 AN: 10354

Middle Eastern (MID) AF: 0.264 AC: 76 AN: 288

European-Non Finnish (NFE) AF: 0.224 AC: 15239 AN: 67888

Other (OTH) AF: 0.289 AC: 606 AN: 2094

Alfa AF: 0.251 Hom.: 655

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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