rs11140213

Variant names:

• chr9-83686569-C-T
• rs11140213
• NM_013438.5:c.181-414G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013438.5(UBQLN1):​c.181-414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,076 control chromosomes in the GnomAD database, including 3,144 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 0.20 (3144 hom., cov: 32)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 1 publications found

Genes affected

UBQLN1 (HGNC:12508): (ubiquilin 1) This gene encodes an ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to modulate accumulation of presenilin proteins, and it is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBQLN1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.181-414G>A		intron_variant	Intron 1 of 10	ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.181-414G>A		intron_variant	Intron 1 of 9		NP_444295.1
UBQLN1	XM_005251948.4	c.181-414G>A		intron_variant	Intron 1 of 7		XP_005252005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.181-414G>A		intron_variant	Intron 1 of 10	1	NM_013438.5	ENSP00000365576.4
UBQLN1	ENST00000257468.11	c.181-414G>A		intron_variant	Intron 1 of 9	1		ENSP00000257468.7
UBQLN1	ENST00000529923.1	c.103-7970G>A		intron_variant	Intron 1 of 2	2		ENSP00000434194.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29731 AN: 151960 Hom.: 3145 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29738 AN: 152076 Hom.: 3144 Cov.: 32 AF XY: 0.194 AC XY: 14434 AN XY: 74316

African (AFR) AF: 0.246 AC: 10192 AN: 41460

American (AMR) AF: 0.139 AC: 2124 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2046 AN: 10558

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12861 AN: 67992

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.193 Hom.: 382

Bravo AF: 0.192

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.67
PhyloP100		0.58
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: rs11140213; hg19: chr9-86301484;