6-169753606-A-C

Position:

• chr6-169753606-A-C

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.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

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=-0.87).
• BP6: Variant 6-169753606-A-C is Benign according to our data. Variant chr6-169753606-A-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERMARD	NM_018341.3	c.7-258A>C		intron_variant		ENST00000366773.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMARD	ENST00000366773.8	c.7-258A>C		intron_variant		2	NM_018341.3	P2

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0977

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0817 Hom.: 189

Bravo AF: 0.102

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.76

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: rs2274953; hg19: chr6-170153702; COSMIC: COSV64649729; COSMIC: COSV64649729;