GeneBe

rs370025001

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000252108.8(UBE4A):​c.2412+3_2412+15delAAAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,067,142 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000038 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

UBE4A
ENST00000252108.8 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Publications

1 publications found
Variant links:
Genes affected
UBE4A (HGNC:12499): (ubiquitination factor E4A) This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]
UBE4A Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with hypotonia and gross motor and speech delay
    Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • multiple congenital anomalies/dysmorphic syndrome
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252108.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
UBE4A
NM_001204077.2
MANE Select
c.2412+11_2412+23delAAAAAAAAAAAAA
intron
N/ANP_001191006.1Q14139-1
UBE4A
NM_004788.4
c.2433+11_2433+23delAAAAAAAAAAAAA
intron
N/ANP_004779.2
LOC100131626
NR_046369.1
n.232-3400_232-3388delTTTTTTTTTTTTT
intron
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
UBE4A
ENST00000252108.8
TSL:1 MANE Select
c.2412+3_2412+15delAAAAAAAAAAAAA
splice_region intron
N/AENSP00000252108.4Q14139-1
UBE4A
ENST00000431736.6
TSL:1
c.2433+3_2433+15delAAAAAAAAAAAAA
splice_region intron
N/AENSP00000387362.2Q14139-2
UBE4A
ENST00000911347.1
c.2430+3_2430+15delAAAAAAAAAAAAA
splice_region intron
N/AENSP00000581406.1

Frequencies

GnomAD3 genomes
AF:
0.0000377
AC:
3
AN:
79516
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000915
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000267
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000132
AC:
13
AN:
987626
Hom.:
0
AF XY:
0.0000199
AC XY:
10
AN XY:
503546
show subpopulations
African (AFR)
AF:
0.0000899
AC:
2
AN:
22242
American (AMR)
AF:
0.00
AC:
0
AN:
28600
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18950
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34804
South Asian (SAS)
AF:
0.00
AC:
0
AN:
63528
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34472
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3898
European-Non Finnish (NFE)
AF:
0.0000136
AC:
10
AN:
738006
Other (OTH)
AF:
0.0000232
AC:
1
AN:
43126
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.671
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
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:
0.0000377
AC:
3
AN:
79516
Hom.:
0
Cov.:
29
AF XY:
0.0000265
AC XY:
1
AN XY:
37764
show subpopulations
African (AFR)
AF:
0.0000915
AC:
2
AN:
21850
American (AMR)
AF:
0.00
AC:
0
AN:
6906
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2000
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2948
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2578
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4192
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
130
European-Non Finnish (NFE)
AF:
0.0000267
AC:
1
AN:
37442
Other (OTH)
AF:
0.00
AC:
0
AN:
1018
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.558
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
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
Alfa
AF:
0.00
Hom.:
14
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.1

Splicing

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

Publications

Other links and lift over

dbSNP: rs370025001; hg19: chr11-118255662; API