rs6589663

Positions:

• chr11-118384563-G-A
• chr11-118384563-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204077.2(UBE4A):​c.2198-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,387,392 control chromosomes in the GnomAD database, including 63,807 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: 𝑓 0.30 (7021 hom., cov: 31)
  • Exomes 𝑓: 0.29 (56786 hom.)
• Consequence: UBE4A NM_001204077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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]

LOC100131626 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4A	NM_001204077.2	c.2198-72G>A		intron_variant		ENST00000252108.8
LOC100131626	NR_046370.1	n.232-3056C>T		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2219-72G>A		intron_variant
LOC100131626	NR_046369.1	n.232-3003C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE4A	ENST00000252108.8	c.2198-72G>A		intron_variant		1	NM_001204077.2	P1
UBE4A	ENST00000431736.6	c.2219-72G>A		intron_variant		1
UBE4A	ENST00000545354.1	c.614-72G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44914 AN: 151804 Hom.: 7020 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.291 AC: 360116 AN: 1235468 Hom.: 56786 AF XY: 0.298 AC XY: 185591 AN XY: 621954

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.296 AC: 44958 AN: 151924 Hom.: 7021 Cov.: 31 AF XY: 0.304 AC XY: 22561 AN XY: 74262

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.273

Alfa AF: 0.261 Hom.: 5681

Bravo AF: 0.289

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs6589663; hg19: chr11-118255278; COSMIC: COSV52802997;