Variant rs370025001 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001204077.2(UBE4A):c.2412+11_2412+23del variant causes a splice donor 5th base, 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. 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
NM_001204077.2 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

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 links:

LOC100131626 (HGNC:):

LOC100131626 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
UBE4A	NM_001204077.2 linkuse as main transcript	c.2412+11_2412+23del	splice_donor_5th_base_variant, intron_variant	ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1 linkuse as main transcript	n.232-3453_232-3441del	intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4 linkuse as main transcript	c.2433+11_2433+23del	splice_donor_5th_base_variant, intron_variant		NP_004779.2
LOC100131626	NR_046369.1 linkuse as main transcript	n.232-3400_232-3388del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8 linkuse as main transcript	c.2412+11_2412+23del	splice_donor_5th_base_variant, intron_variant	1	NM_001204077.2	ENSP00000252108	P1	Q14139-1
UBE4A	ENST00000431736.6 linkuse as main transcript	c.2433+11_2433+23del	splice_donor_5th_base_variant, intron_variant	1		ENSP00000387362		Q14139-2
UBE4A	ENST00000545354.1 linkuse as main transcript	c.828+11_828+23del	splice_donor_5th_base_variant, intron_variant	2		ENSP00000438918

Frequencies

GnomAD3 genomes

AF:

0.0000377

AC:

AN:

79516

Hom.:

Cov.:

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:

AN:

987626

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

503546

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000232

GnomAD4 genome

AF:

0.0000377

AC:

AN:

79516

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

37764

show subpopulations

Gnomad4 AFR

AF:

0.0000915

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000267

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over