rs6503965

chr17-60396954-T-C

Variant summary

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

The ENST00000588898.1(USP32):c.106+25292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,152 control chromosomes in the GnomAD database, including 12,856 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 0.31 (12856 hom., cov: 32)
• Consequence: USP32 ENST00000588898.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

Genes affected

CHCT1 (HGNC:26990): (CHD1 helical C-terminal domain containing 1)

USP32 (HGNC:19143): (ubiquitin specific peptidase 32) Enables thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP32	XM_011525371.2	c.106+25292A>G		intron_variant
USP32	XM_011525372.2	c.106+25292A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHCT1	ENST00000461535.1	c.-61+4412T>C		intron_variant		2
USP32	ENST00000588898.1	c.106+25292A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46297 AN: 152034 Hom.: 12795 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.305 AC: 46416 AN: 152152 Hom.: 12856 Cov.: 32 AF XY: 0.297 AC XY: 22126 AN XY: 74402

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.257

Alfa AF: 0.159 Hom.: 3212

Bravo AF: 0.333

Asia WGS AF: 0.265 AC: 922 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	1.9
Dann	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6503965; hg19: chr17-58474315;