chr6-169753606-A-C

Variant names:

• chr6-169753606-A-C
• rs2274953
• NM_018341.3:c.7-258A>C

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.7-258A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,008 control chromosomes in the GnomAD database, including 790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.099 (790 hom., cov: 32)
• Consequence: ERMARD NM_018341.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• 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, LIMITED Submitted by: ClinGen, Orphanet
• periventricular nodular heterotopia 6

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-169753606-A-C is Benign according to our data. Variant chr6-169753606-A-C is described in ClinVar as Benign. ClinVar VariationId is 1242689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMARD	NM_018341.3	MANE Select	c.7-258A>C		intron	N/A	NP_060811.1	Q5T6L9-1
	ERMARD	NM_001278531.2		c.7-258A>C		intron	N/A	NP_001265460.1	Q5T6L9-3
	ERMARD	NM_001278533.2		c.7-258A>C		intron	N/A	NP_001265462.1	Q5T6L9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMARD	ENST00000366773.8	TSL:2 MANE Select	c.7-258A>C		intron	N/A	ENSP00000355735.3	Q5T6L9-1
	ERMARD	ENST00000418781.7	TSL:1	c.7-258A>C		intron	N/A	ENSP00000397661.2	Q5T6L9-2
	ERMARD	ENST00000854211.1		c.7-258A>C		intron	N/A	ENSP00000524270.1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15031 AN: 151890 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0977

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0990 AC: 15045 AN: 152008 Hom.: 790 Cov.: 32 AF XY: 0.0969 AC XY: 7202 AN XY: 74298

African (AFR) AF: 0.107 AC: 4431 AN: 41464

American (AMR) AF: 0.0977 AC: 1491 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3468

East Asian (EAS) AF: 0.0380 AC: 197 AN: 5178

South Asian (SAS) AF: 0.0702 AC: 338 AN: 4814

European-Finnish (FIN) AF: 0.0620 AC: 654 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7181 AN: 67946

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0862 Hom.: 258

Bravo AF: 0.102

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		1.4
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: rs2274953; hg19: chr6-170153702; COSMIC: COSV64649729; COSMIC: COSV64649729;