18-203081-A-C

Position:

• chr18-203081-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005151.4(USP14):​c.943-17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,610,942 control chromosomes in the GnomAD database, including 320,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29083 hom., cov: 33)
  • Exomes 𝑓: 0.63 (291125 hom.)
• Consequence: USP14 NM_005151.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.264

Genes affected

USP14 (HGNC:12612): (ubiquitin specific peptidase 14) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

USP14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-203081-A-C is Benign according to our data. Variant chr18-203081-A-C is described in ClinVar as [Benign]. Clinvar id is 1226537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP14	NM_005151.4	c.943-17A>C		intron_variant		ENST00000261601.8	NP_005142.1
USP14	NM_001037334.2	c.838-17A>C		intron_variant			NP_001032411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP14	ENST00000261601.8	c.943-17A>C		intron_variant		1	NM_005151.4	ENSP00000261601.6

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93537 AN: 151894 Hom.: 29034 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.595

GnomAD3 exomes AF: 0.647 AC: 161284 AN: 249124 Hom.: 53260 AF XY: 0.648 AC XY: 87269 AN XY: 134648

Gnomad AFR exome AF: 0.580

Gnomad AMR exome AF: 0.764

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.559

Gnomad SAS exome AF: 0.758

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.622

Gnomad OTH exome AF: 0.616

GnomAD4 exome AF: 0.630 AC: 918653 AN: 1458930 Hom.: 291125 Cov.: 39 AF XY: 0.632 AC XY: 458726 AN XY: 725600

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.753

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.748

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.616 AC: 93648 AN: 152012 Hom.: 29083 Cov.: 33 AF XY: 0.620 AC XY: 46096 AN XY: 74292

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.599

Alfa AF: 0.612 Hom.: 5878

Bravo AF: 0.614

Asia WGS AF: 0.697 AC: 2422 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.43

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: rs471274; hg19: chr18-203081;