Variant X-154379351-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000117.3(EMD):c.-134A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 638,444 control chromosomes in the GnomAD database, including 6 homozygotes. There are 210 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., 160 hem., cov: 26)

Exomes 𝑓: 0.00036 ( 1 hom. 50 hem. )

Consequence

EMD
NM_000117.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.666

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-154379351-A-G is Benign according to our data. Variant chrX-154379351-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1209222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (581/113324) while in subpopulation AFR AF= 0.018 (564/31331). AF 95% confidence interval is 0.0168. There are 5 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMD	NM_000117.3 linkuse as main transcript	c.-134A>G		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.-134A>G	5_prime_UTR_variant	1/6	1	NM_000117.3	ENSP00000358857	P1
EMD	ENST00000369835.3 linkuse as main transcript	c.-134A>G	5_prime_UTR_variant	1/5	3		ENSP00000358850
EMD	ENST00000486738.5 linkuse as main transcript	n.11A>G	non_coding_transcript_exon_variant	1/4	3
EMD	ENST00000428228.5 linkuse as main transcript		upstream_gene_variant		3		ENSP00000401081

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

582

AN:

113275

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

160

AN XY:

35497

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000732

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000350

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000751

Gnomad OTH

AF:

0.00328

GnomAD4 exome

AF:

0.000364

AC:

191

AN:

525120

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

AN XY:

146744

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.000371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000316

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000265

Gnomad4 OTH exome

AF:

0.000461

GnomAD4 genome

AF:

0.00513

AC:

581

AN:

113324

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

160

AN XY:

35556

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.000640

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000351

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00323

Alfa

AF:

0.00377

Hom.:

Bravo

AF:

0.00543

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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