rs2781003

Variant names:

• chr9-83664100-C-T
• rs2781003
• NM_013438.5:c.1449-57G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-83664100-C-T
• chr9-83664100-C-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.1449-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,547,714 control chromosomes in the GnomAD database, including 329,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.70 (38348 hom., cov: 32)
  • Exomes 𝑓: 0.64 (291493 hom.)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	NM_013438.5	MANE Select	c.1449-57G>A		intron	N/A	NP_038466.2
	UBQLN1	NM_053067.3		c.1365-57G>A		intron	N/A	NP_444295.1	Q9UMX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	ENST00000376395.9	TSL:1 MANE Select	c.1449-57G>A		intron	N/A	ENSP00000365576.4	Q9UMX0-1
	UBQLN1	ENST00000257468.11	TSL:1	c.1365-57G>A		intron	N/A	ENSP00000257468.7	Q9UMX0-2
	UBQLN1	ENST00000533705.5	TSL:1	n.3918-57G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106662 AN: 151902 Hom.: 38315 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.643 AC: 896890 AN: 1395694 Hom.: 291493 AF XY: 0.644 AC XY: 445591 AN XY: 691992

African (AFR) AF: 0.847 AC: 26103 AN: 30826

American (AMR) AF: 0.741 AC: 25869 AN: 34918

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 15830 AN: 22754

East Asian (EAS) AF: 0.884 AC: 34522 AN: 39054

South Asian (SAS) AF: 0.725 AC: 56713 AN: 78248

European-Finnish (FIN) AF: 0.573 AC: 29574 AN: 51614

Middle Eastern (MID) AF: 0.724 AC: 3803 AN: 5254

European-Non Finnish (NFE) AF: 0.619 AC: 665987 AN: 1075522

Other (OTH) AF: 0.669 AC: 38489 AN: 57504

GnomAD4 genome AF: 0.702 AC: 106750 AN: 152020 Hom.: 38348 Cov.: 32 AF XY: 0.702 AC XY: 52143 AN XY: 74316

African (AFR) AF: 0.840 AC: 34854 AN: 41484

American (AMR) AF: 0.708 AC: 10828 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2432 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4573 AN: 5174

South Asian (SAS) AF: 0.731 AC: 3530 AN: 4828

European-Finnish (FIN) AF: 0.585 AC: 6168 AN: 10538

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41998 AN: 67922

Other (OTH) AF: 0.718 AC: 1514 AN: 2110

Alfa AF: 0.668 Hom.: 5375

Bravo AF: 0.721

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.59
PhyloP100		-0.42
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: rs2781003; hg19: chr9-86279015;