16-58020561-C-CCTCT

Position:

• chr16-58020561-C-CCTCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024598.4(USB1):​c.*319_*322dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (55552 hom., cov: 0)
  • Exomes 𝑓: 0.96 (104435 hom.)
• Consequence: USB1 NM_024598.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550

Genes affected

USB1 (HGNC:25792): (U6 snRNA biogenesis phosphodiesterase 1) This gene encodes a protein with several conserved domains, however, its exact function is not known. Mutations in this gene are associated with poikiloderma with neutropenia (PN), which shows phenotypic overlap with Rothmund-Thomson syndrome (RTS) caused by mutations in the RECQL4 gene. It is believed that this gene product interacts with RECQL4 protein via SMAD4 proteins, explaining the partial clinical overlap between PN and RTS. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-58020561-C-CCTCT is Benign according to our data. Variant chr16-58020561-C-CCTCT is described in ClinVar as [Likely_benign]. Clinvar id is 212550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USB1	NM_024598.4	c.*319_*322dup		3_prime_UTR_variant	7/7	ENST00000219281.8	NP_078874.2
USB1	NM_001195302.2	c.*319_*322dup		3_prime_UTR_variant	6/6		NP_001182231.1
USB1	NM_001330568.2	c.*319_*322dup		3_prime_UTR_variant	7/7		NP_001317497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USB1	ENST00000219281.8	c.*319_*322dup		3_prime_UTR_variant	7/7	1	NM_024598.4	ENSP00000219281

Frequencies

GnomAD3 genomes AF: 0.950 AC: 116764 AN: 122910 Hom.: 55495 Cov.: 0

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.976

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.948

GnomAD4 exome AF: 0.955 AC: 218550 AN: 228760 Hom.: 104435 Cov.: 0 AF XY: 0.957 AC XY: 118598 AN XY: 123910

Gnomad4 AFR exome AF: 0.948

Gnomad4 AMR exome AF: 0.969

Gnomad4 ASJ exome AF: 0.957

Gnomad4 EAS exome AF: 0.980

Gnomad4 SAS exome AF: 0.974

Gnomad4 FIN exome AF: 0.967

Gnomad4 NFE exome AF: 0.946

Gnomad4 OTH exome AF: 0.952

GnomAD4 genome AF: 0.950 AC: 116886 AN: 123042 Hom.: 55552 Cov.: 0 AF XY: 0.951 AC XY: 55652 AN XY: 58518

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.947

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 30, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58782258; hg19: chr16-58054465;