Variant X-154379314-CGTGACGCGACAACGATTCGGCT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000117.3(EMD):c.-139_-118del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 487,802 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 26)

Exomes 𝑓: 0.00024 ( 0 hom. 30 hem. )

Consequence

EMD
NM_000117.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

EMD (HGNC:3331): (emerin) Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Dreifuss-Emery muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the emerin gene. [provided by RefSeq, Jul 2008]

EMD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-154379314-CGTGACGCGACAACGATTCGGCT-C is Benign according to our data. Variant chrX-154379314-CGTGACGCGACAACGATTCGGCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1215766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000114 (13/113626) while in subpopulation EAS AF= 0.000841 (3/3569). AF 95% confidence interval is 0.000228. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMD	NM_000117.3 linkuse as main transcript	c.-139_-118del		5_prime_UTR_variant	1/6	ENST00000369842.9	NP_000108.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
EMD	ENST00000369842.9 linkuse as main transcript	c.-139_-118del	5_prime_UTR_variant	1/6	1	NM_000117.3	ENSP00000358857	P1
EMD	ENST00000369835.3 linkuse as main transcript	c.-139_-118del	5_prime_UTR_variant	1/5	3		ENSP00000358850
EMD	ENST00000428228.5 linkuse as main transcript		upstream_gene_variant		3		ENSP00000401081
EMD	ENST00000486738.5 linkuse as main transcript		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000114

AC:

AN:

113578

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

35760

show subpopulations

Gnomad AFR

AF:

0.000191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000838

Gnomad SAS

AF:

0.000347

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000562

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000241

AC:

AN:

374176

Hom.:

AF XY:

0.000263

AC XY:

AN XY:

114084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000828

Gnomad4 SAS exome

AF:

0.000356

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.000295

GnomAD4 genome

AF:

0.000114

AC:

AN:

113626

Hom.:

Cov.:

AF XY:

0.0000838

AC XY:

AN XY:

35818

show subpopulations

Gnomad4 AFR

AF:

0.000191

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000841

Gnomad4 SAS

AF:

0.000348

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2020

This variant is associated with the following publications: (PMID: 9536090, 9195226) -

X-linked Emery-Dreifuss muscular dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2022

- -

EMD-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over