rs4716396

Variant names:

• chr6-169773818-T-C
• rs4716396
• NM_018341.3:c.1317+416T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018341.3(ERMARD):​c.1317+416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,072 control chromosomes in the GnomAD database, including 8,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8008 hom., cov: 33)
• Consequence: ERMARD NM_018341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 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.1317+416T>C		intron	N/A	NP_060811.1	Q5T6L9-1
	ERMARD	NM_001278531.2		c.1317+416T>C		intron	N/A	NP_001265460.1	Q5T6L9-3
	ERMARD	NM_001278533.2		c.1317+416T>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.1317+416T>C		intron	N/A	ENSP00000355735.3	Q5T6L9-1
	ERMARD	ENST00000418781.7	TSL:1	c.1317+416T>C		intron	N/A	ENSP00000397661.2	Q5T6L9-2
	ERMARD	ENST00000854211.1		c.1317+416T>C		intron	N/A	ENSP00000524270.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45775 AN: 151954 Hom.: 7971 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.302 AC: 45878 AN: 152072 Hom.: 8008 Cov.: 33 AF XY: 0.298 AC XY: 22147 AN XY: 74322

African (AFR) AF: 0.479 AC: 19864 AN: 41468

American (AMR) AF: 0.275 AC: 4193 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1693 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10584

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15267 AN: 67972

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.273 Hom.: 805

Bravo AF: 0.319

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-0.051
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: rs4716396; hg19: chr6-170173914;