rs6589663

Variant names:

• chr11-118384563-G-A
• rs6589663
• NM_001204077.2:c.2198-72G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

LOC100131626 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2198-72G>A		intron_variant	Intron 13 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.2219-72G>A		intron_variant	Intron 13 of 19		NP_004779.2
LOC100131626	NR_046369.1	n.232-3003C>T		intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1	n.232-3056C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8	c.2198-72G>A		intron_variant	Intron 13 of 19	1	NM_001204077.2	ENSP00000252108.4
UBE4A	ENST00000431736.6	c.2219-72G>A		intron_variant	Intron 13 of 19	1		ENSP00000387362.2
UBE4A	ENST00000545354.1	c.614-72G>A		intron_variant	Intron 4 of 10	2		ENSP00000438918.1

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

African (AFR) AF: 0.316 AC: 8855 AN: 28060

American (AMR) AF: 0.196 AC: 7590 AN: 38788

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 8303 AN: 23228

East Asian (EAS) AF: 0.584 AC: 22133 AN: 37920

South Asian (SAS) AF: 0.503 AC: 39370 AN: 78268

European-Finnish (FIN) AF: 0.282 AC: 14618 AN: 51778

Middle Eastern (MID) AF: 0.332 AC: 1713 AN: 5152

European-Non Finnish (NFE) AF: 0.262 AC: 241259 AN: 919688

Other (OTH) AF: 0.309 AC: 16275 AN: 52586

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

African (AFR) AF: 0.317 AC: 13101 AN: 41386

American (AMR) AF: 0.242 AC: 3693 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2978 AN: 5168

South Asian (SAS) AF: 0.508 AC: 2447 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3110 AN: 10534

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17578 AN: 67970

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.264 Hom.: 7677

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
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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