Genetic Variant USB1:c.*319_*322dupCTCT (chr16-58020561-C-CCTCT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_024598.4(USB1):c.*319_*322dupCTCT 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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0550

Variant links:

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]

USB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
USB1	NM_024598.4 link	c.319_322dupCTCT	3_prime_UTR_variant	Exon 7 of 7	ENST00000219281.8	NP_078874.2	Q9BQ65-1A0A024R6V6
USB1	NM_001195302.2 link	c.319_322dupCTCT	3_prime_UTR_variant	Exon 6 of 6		NP_001182231.1	Q9BQ65-2
USB1	NM_001330568.2 link	c.319_322dupCTCT	3_prime_UTR_variant	Exon 7 of 7		NP_001317497.1	Q9BQ65H3BNM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USB1	ENST00000219281.8 link	c.319_322dupCTCT		3_prime_UTR_variant	Exon 7 of 7	1	NM_024598.4	ENSP00000219281.3		Q9BQ65-1

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

116764

AN:

122910

Hom.:

55495

Cov.:

show subpopulations

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.:

AF XY:

0.957

AC XY:

118598

AN XY:

123910

show subpopulations

Gnomad4 AFR exome

AF:

0.948

AC:

6121

AN:

6456

Gnomad4 AMR exome

AF:

0.969

AC:

10653

AN:

10996

Gnomad4 ASJ exome

AF:

0.957

AC:

5752

AN:

6008

Gnomad4 EAS exome

AF:

0.980

AC:

10761

AN:

10984

Gnomad4 SAS exome

AF:

0.974

AC:

39747

AN:

40794

Gnomad4 FIN exome

AF:

0.967

AC:

10110

AN:

10460

Gnomad4 NFE exome

AF:

0.946

AC:

123294

AN:

130354

Gnomad4 Remaining exome

AF:

0.952

AC:

11264

AN:

11834

Heterozygous variant carriers

453

905

1358

1810

2263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.950

AC:

116886

AN:

123042

Hom.:

55552

Cov.:

AF XY:

0.951

AC XY:

55652

AN XY:

58518

show subpopulations

Gnomad4 AFR

AF:

0.948

AC:

0.948171

AN:

0.948171

Gnomad4 AMR

AF:

0.962

AC:

0.962181

AN:

0.962181

Gnomad4 ASJ

AF:

0.960

AC:

0.959791

AN:

0.959791

Gnomad4 EAS

AF:

0.977

AC:

0.976912

AN:

0.976912

Gnomad4 SAS

AF:

0.977

AC:

0.976737

AN:

0.976737

Gnomad4 FIN

AF:

0.966

AC:

0.966236

AN:

0.966236

Gnomad4 NFE

AF:

0.943

AC:

0.942878

AN:

0.942878

Gnomad4 OTH

AF:

0.947

AC:

0.946882

AN:

0.946882

Heterozygous variant carriers

243

487

730

974

1217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 30, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 17, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over