rs2304446

Positions:

• chr17-5145110-G-A
• chr17-5145110-G-T

Variant summary

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

The NM_001304284.2(USP6):​c.1992+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,048 control chromosomes in the GnomAD database, including 43,802 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 0.75 (43802 hom., cov: 31)
• Consequence: USP6 NM_001304284.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

Genes affected

USP6 (HGNC:12629): (ubiquitin specific peptidase 6) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination and regulation of vesicle-mediated transport. Located in plasma membrane and recycling endosome. [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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP6	NM_001304284.2	c.1992+247G>A		intron_variant		ENST00000574788.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP6	ENST00000574788.6	c.1992+247G>A		intron_variant		1	NM_001304284.2	P1
USP6	ENST00000250066.6	c.1992+247G>A		intron_variant		1		P1
USP6	ENST00000572949.5	c.1992+247G>A		intron_variant, NMD_transcript_variant		2
USP6	ENST00000575709.5	c.*1072+247G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114304 AN: 151930 Hom.: 43790 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.752 AC: 114366 AN: 152048 Hom.: 43802 Cov.: 31 AF XY: 0.743 AC XY: 55207 AN XY: 74298

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.762

Alfa AF: 0.746 Hom.: 4065

Bravo AF: 0.753

Asia WGS AF: 0.398 AC: 1387 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.5
DANN	Benign	0.42

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: rs2304446; hg19: chr17-5048405;