11-118371609-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS1

The NM_001204077.2(UBE4A):​c.504A>G​(p.Ala168Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,613,942 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.00085 ( 1 hom., cov: 32)
Exomes š‘“: 0.00018 ( 1 hom. )

Consequence

UBE4A
NM_001204077.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP7
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000853 (130/152348) while in subpopulation AFR AF= 0.00255 (106/41574). AF 95% confidence interval is 0.00216. There are 1 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBE4ANM_001204077.2 linkc.504A>G p.Ala168Ala synonymous_variant Exon 5 of 20 ENST00000252108.8 NP_001191006.1
UBE4ANM_004788.4 linkc.504A>G p.Ala168Ala synonymous_variant Exon 5 of 20 NP_004779.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBE4AENST00000252108.8 linkc.504A>G p.Ala168Ala synonymous_variant Exon 5 of 20 1 NM_001204077.2 ENSP00000252108.4 Q14139-1
UBE4AENST00000431736.6 linkc.504A>G p.Ala168Ala synonymous_variant Exon 5 of 20 1 ENSP00000387362.2 Q14139-2

Frequencies

GnomAD3 genomes
AF:
0.000854
AC:
130
AN:
152230
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00256
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000350
AC:
88
AN:
251088
Hom.:
1
AF XY:
0.000302
AC XY:
41
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.00258
Gnomad AMR exome
AF:
0.000637
Gnomad ASJ exome
AF:
0.000596
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000183
AC:
268
AN:
1461594
Hom.:
1
Cov.:
30
AF XY:
0.000180
AC XY:
131
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.00314
Gnomad4 AMR exome
AF:
0.000582
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000656
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.000853
AC:
130
AN:
152348
Hom.:
1
Cov.:
32
AF XY:
0.000765
AC XY:
57
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00255
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000474
Hom.:
0
Bravo
AF:
0.000842
EpiCase
AF:
0.000436
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not provided Benign:1
Mar 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

UBE4A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
8.1
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs145949976; hg19: chr11-118242324; API