X-154379461-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000117.3(EMD):​c.-24C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000946 in 1,162,784 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000018 ( 0 hom., 1 hem., cov: 26)
Exomes 𝑓: 0.0000086 ( 0 hom. 5 hem. )

Consequence

EMD
NM_000117.3 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.151

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • X-linked Emery-Dreifuss muscular dystrophy
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • heart conduction disease
    Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant X-154379461-C-T is Benign according to our data. Variant chrX-154379461-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382185.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000858 (9/1049022) while in subpopulation AMR AF = 0.000287 (8/27831). AF 95% confidence interval is 0.000143. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EMDNM_000117.3 linkc.-24C>T 5_prime_UTR_variant Exon 1 of 6 ENST00000369842.9 NP_000108.1 P50402

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EMDENST00000369842.9 linkc.-24C>T 5_prime_UTR_variant Exon 1 of 6 1 NM_000117.3 ENSP00000358857.4 P50402

Frequencies

GnomAD3 genomes
AF:
0.0000176
AC:
2
AN:
113715
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000279
AC:
3
AN:
107697
AF XY:
0.0000538
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000156
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000858
AC:
9
AN:
1049022
Hom.:
0
Cov.:
31
AF XY:
0.0000146
AC XY:
5
AN XY:
342126
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24451
American (AMR)
AF:
0.000287
AC:
8
AN:
27831
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18531
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26864
South Asian (SAS)
AF:
0.0000201
AC:
1
AN:
49676
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36449
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3913
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
817164
Other (OTH)
AF:
0.00
AC:
0
AN:
44143
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.538
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000176
AC:
2
AN:
113762
Hom.:
0
Cov.:
26
AF XY:
0.0000278
AC XY:
1
AN XY:
35926
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31492
American (AMR)
AF:
0.000183
AC:
2
AN:
10925
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2659
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3601
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2872
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6391
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
217
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53370
Other (OTH)
AF:
0.00
AC:
0
AN:
1551
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000453

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 13, 2017
GeneDx
Significance:Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
9.5
DANN
Benign
0.84
PhyloP100
0.15
PromoterAI
-0.26
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Mutation Taster
=300/0
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

Other links and lift over

dbSNP: rs958112509; hg19: chrX-153607821; API