6-169753866-A-C

Variant names:

• chr6-169753866-A-C
• rs61736820
• NM_018341.3:c.9A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018341.3(ERMARD):​c.9A>C​(p.Val3Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,552,726 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (50 hom.)
• Consequence: ERMARD NM_018341.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0670

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-169753866-A-C is Benign according to our data. Variant chr6-169753866-A-C is described in ClinVar as [Benign]. Clinvar id is 384836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-169753866-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.067 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2081/152222) while in subpopulation AFR AF = 0.0471 (1957/41538). AF 95% confidence interval is 0.0454. There are 43 homozygotes in GnomAd4. There are 1016 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 2081 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMARD	NM_018341.3	c.9A>C	p.Val3Val	splice_region_variant, synonymous_variant	Exon 2 of 18	ENST00000366773.8	NP_060811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMARD	ENST00000366773.8	c.9A>C	p.Val3Val	splice_region_variant, synonymous_variant	Exon 2 of 18	2	NM_018341.3	ENSP00000355735.3

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2069 AN: 152104 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00364 AC: 656 AN: 180184 AF XY: 0.00248

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00251

Gnomad ASJ exome AF: 0.000245

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00107

GnomAD4 exome AF: 0.00143 AC: 2005 AN: 1400504 Hom.: 50 Cov.: 30 AF XY: 0.00118 AC XY: 818 AN XY: 693532

Gnomad4 AFR exome AF: 0.0498 AC: 1533 AN: 30806

Gnomad4 AMR exome AF: 0.00284 AC: 100 AN: 35268

Gnomad4 ASJ exome AF: 0.000204 AC: 5 AN: 24500

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 36648

Gnomad4 SAS exome AF: 0.000151 AC: 12 AN: 79546

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49552

Gnomad4 NFE exome AF: 0.0000999 AC: 108 AN: 1081058

Gnomad4 Remaining exome AF: 0.00414 AC: 239 AN: 57696

GnomAD4 genome AF: 0.0137 AC: 2081 AN: 152222 Hom.: 43 Cov.: 32 AF XY: 0.0136 AC XY: 1016 AN XY: 74442

Gnomad4 AFR AF: 0.0471 AC: 0.0471135 AN: 0.0471135

Gnomad4 AMR AF: 0.00582 AC: 0.00581928 AN: 0.00581928

Gnomad4 ASJ AF: 0.000288 AC: 0.000288184 AN: 0.000288184

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000176 AC: 0.000176465 AN: 0.000176465

Gnomad4 OTH AF: 0.00993 AC: 0.00993377 AN: 0.00993377

Alfa AF: 0.00448 Hom.: 7

Bravo AF: 0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 16, 2016

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. -

not provided Benign:1

Dec 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.065
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism

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: rs61736820; hg19: chr6-170153962;