rs7862315

Variant names:

• chr9-129856528-G-A
• rs7862315
• NM_001110303.4:c.135+168G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-129856528-G-A
• chr9-129856528-G-C

Variant summary

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

The NM_001110303.4(USP20):​c.135+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,312 control chromosomes in the GnomAD database, including 57,235 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 0.86 (57235 hom., cov: 34)
• Consequence: USP20 NM_001110303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

USP20 (HGNC:12619): (ubiquitin specific peptidase 20) This gene encodes a ubiquitin specific processing protease that was first identified as a substrate of the VHL (von Hippel-Lindau disease) protein E3 ubiquitin ligase complex. In addition to being ubiquitinated by the VHL-E3 ligase complex, this enzyme deubiquitinates hypoxia-inducible factor (HIF)-1 alpha and thereby causes increased expression of HIF-1alpha targeted genes which play a role in angiogenesis, glucose metabolism, cell proliferation and metastasis. The enzyme encoded by this gene also regulates G-protein coupled receptor signaling by mediating the deubiquitination of beta-2 adrenergic receptor (ADRB2). This enzyme is a ubiquitously expressed thiolester hydrolase. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP20	NM_001110303.4	c.135+168G>A		intron_variant	Intron 4 of 25	ENST00000372429.8	NP_001103773.2
USP20	NM_001008563.5	c.135+168G>A		intron_variant	Intron 4 of 25		NP_001008563.2
USP20	NM_006676.8	c.135+168G>A		intron_variant	Intron 4 of 24		NP_006667.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP20	ENST00000372429.8	c.135+168G>A		intron_variant	Intron 4 of 25	1	NM_001110303.4	ENSP00000361506.3
USP20	ENST00000315480.9	c.135+168G>A		intron_variant	Intron 4 of 24	1		ENSP00000313811.4
USP20	ENST00000358355.5	c.135+168G>A		intron_variant	Intron 4 of 25	1		ENSP00000351122.1
USP20	ENST00000494971.2	n.359+168G>A		intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131539 AN: 152194 Hom.: 57198 Cov.: 34

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.864 AC: 131631 AN: 152312 Hom.: 57235 Cov.: 34 AF XY: 0.871 AC XY: 64887 AN XY: 74490

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.862

Alfa AF: 0.896 Hom.: 68304

Bravo AF: 0.856

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.041
DANN	Benign	0.77

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: rs7862315; hg19: chr9-132618807;