rs4716396

Positions:

• chr6-169773818-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERMARD	NM_018341.3	c.1317+416T>C		intron_variant		ENST00000366773.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMARD	ENST00000366773.8	c.1317+416T>C		intron_variant		2	NM_018341.3	P2

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

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.300

Alfa AF: 0.265 Hom.: 733

Bravo AF: 0.319

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.62

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: rs4716396; hg19: chr6-170173914;