chr9-83666280-A-G

Variant names:

• chr9-83666280-A-G
• rs12344615
• NM_013438.5:c.1332+70T>C

Variant summary

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

The NM_013438.5(UBQLN1):​c.1332+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,480,400 control chromosomes in the GnomAD database, including 28,218 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 (3167 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25051 hom.)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 14 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	NM_013438.5	MANE Select	c.1332+70T>C		intron	N/A	NP_038466.2
	UBQLN1	NM_053067.3		c.1249-1135T>C		intron	N/A	NP_444295.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	ENST00000376395.9	TSL:1 MANE Select	c.1332+70T>C		intron	N/A	ENSP00000365576.4
	UBQLN1	ENST00000257468.11	TSL:1	c.1249-1135T>C		intron	N/A	ENSP00000257468.7
	UBQLN1	ENST00000533705.5	TSL:1	n.3801+70T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29821 AN: 152056 Hom.: 3167 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.187 AC: 247769 AN: 1328226 Hom.: 25051 AF XY: 0.190 AC XY: 126679 AN XY: 667962

African (AFR) AF: 0.250 AC: 7679 AN: 30668

American (AMR) AF: 0.0992 AC: 4389 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4523 AN: 25058

East Asian (EAS) AF: 0.000437 AC: 17 AN: 38930

South Asian (SAS) AF: 0.261 AC: 21715 AN: 83068

European-Finnish (FIN) AF: 0.183 AC: 9612 AN: 52530

Middle Eastern (MID) AF: 0.269 AC: 1467 AN: 5454

European-Non Finnish (NFE) AF: 0.189 AC: 187782 AN: 992342

Other (OTH) AF: 0.189 AC: 10585 AN: 55954

GnomAD4 genome AF: 0.196 AC: 29829 AN: 152174 Hom.: 3167 Cov.: 32 AF XY: 0.195 AC XY: 14486 AN XY: 74392

African (AFR) AF: 0.247 AC: 10264 AN: 41494

American (AMR) AF: 0.139 AC: 2124 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2052 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12870 AN: 68004

Other (OTH) AF: 0.183 AC: 386 AN: 2108

Alfa AF: 0.189 Hom.: 7837

Bravo AF: 0.193

Asia WGS AF: 0.0960 AC: 334 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12344615; hg19: chr9-86281195;