rs2238114

Variant names:

• chr12-6856576-C-A
• rs2238114
• NM_001098536.2:c.584+126C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6856576-C-A
• chr12-6856576-C-G
• chr12-6856576-C-T

Variant summary

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

The NM_001098536.2(USP5):​c.584+126C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,542,150 control chromosomes in the GnomAD database, including 96,648 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 0.45 (18350 hom., cov: 31)
  • Exomes 𝑓: 0.32 (78298 hom.)
• Consequence: USP5 NM_001098536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 23 publications found

Genes affected

USP5 (HGNC:12628): (ubiquitin specific peptidase 5) Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098536.2. 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
	USP5	NM_001098536.2	MANE Select	c.584+126C>A		intron	N/A	NP_001092006.1
	USP5	NM_003481.3		c.584+126C>A		intron	N/A	NP_003472.2
	USP5	NM_001382591.1		c.584+126C>A		intron	N/A	NP_001369520.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP5	ENST00000229268.13	TSL:1 MANE Select	c.584+126C>A		intron	N/A	ENSP00000229268.8
	USP5	ENST00000389231.9	TSL:1	c.584+126C>A		intron	N/A	ENSP00000373883.5
	USP5	ENST00000542087.1	TSL:3	c.357+507C>A		intron	N/A	ENSP00000444668.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67825 AN: 151864 Hom.: 18305 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.323 AC: 449711 AN: 1390168 Hom.: 78298 Cov.: 30 AF XY: 0.323 AC XY: 221269 AN XY: 685398

African (AFR) AF: 0.793 AC: 25209 AN: 31780

American (AMR) AF: 0.367 AC: 14117 AN: 38502

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 7440 AN: 22204

East Asian (EAS) AF: 0.515 AC: 20142 AN: 39098

South Asian (SAS) AF: 0.322 AC: 24569 AN: 76346

European-Finnish (FIN) AF: 0.259 AC: 10848 AN: 41960

Middle Eastern (MID) AF: 0.488 AC: 2661 AN: 5456

European-Non Finnish (NFE) AF: 0.301 AC: 324111 AN: 1077250

Other (OTH) AF: 0.358 AC: 20614 AN: 57572

GnomAD4 genome AF: 0.447 AC: 67935 AN: 151982 Hom.: 18350 Cov.: 31 AF XY: 0.442 AC XY: 32790 AN XY: 74262

African (AFR) AF: 0.765 AC: 31720 AN: 41446

American (AMR) AF: 0.412 AC: 6305 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2643 AN: 5154

South Asian (SAS) AF: 0.314 AC: 1516 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2617 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20539 AN: 67936

Other (OTH) AF: 0.459 AC: 967 AN: 2108

Alfa AF: 0.323 Hom.: 4744

Bravo AF: 0.475

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.025
DANN	Benign	0.46
PhyloP100		-1.4
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: rs2238114; hg19: chr12-6965740; COSMIC: COSV57540679; COSMIC: COSV57540679;