rs58782258

Variant names:

• chr16-58020561-C-CCTCT
• rs58782258
• NM_024598.4:c.*319_*322dupCTCT

Your query was ambiguous. Multiple possible variants found:

• chr16-58020561-C-CCTCT
• chr16-58020561-C-CCT
• chr16-58020561-C-CCTCTCTCTCTTCCTCTCCT
• chr16-58020561-C-CCTCTCTCTCTTCCTCTCCTCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• poikiloderma with neutropenia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• dyskeratosis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USB1	NM_024598.4	MANE Select	c.*319_*322dupCTCT		3_prime_UTR	Exon 7 of 7	NP_078874.2
	USB1	NM_001195302.2		c.*319_*322dupCTCT		3_prime_UTR	Exon 6 of 6	NP_001182231.1	Q9BQ65-2
	USB1	NM_001330568.2		c.*319_*322dupCTCT		3_prime_UTR	Exon 7 of 7	NP_001317497.1	H3BNM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USB1	ENST00000219281.8	TSL:1 MANE Select	c.*319_*322dupCTCT		3_prime_UTR	Exon 7 of 7	ENSP00000219281.3	Q9BQ65-1
	USB1	ENST00000561568.6	TSL:4	c.*319_*322dupCTCT		3_prime_UTR	Exon 7 of 7	ENSP00000457322.2	H3BTT8
	USB1	ENST00000539737.6	TSL:2	c.*319_*322dupCTCT		3_prime_UTR	Exon 6 of 6	ENSP00000446143.2	Q9BQ65-2

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

African (AFR) AF: 0.948 AC: 6121 AN: 6456

American (AMR) AF: 0.969 AC: 10653 AN: 10996

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 5752 AN: 6008

East Asian (EAS) AF: 0.980 AC: 10761 AN: 10984

South Asian (SAS) AF: 0.974 AC: 39747 AN: 40794

European-Finnish (FIN) AF: 0.967 AC: 10110 AN: 10460

Middle Eastern (MID) AF: 0.970 AC: 848 AN: 874

European-Non Finnish (NFE) AF: 0.946 AC: 123294 AN: 130354

Other (OTH) AF: 0.952 AC: 11264 AN: 11834

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

African (AFR) AF: 0.948 AC: 28612 AN: 30176

American (AMR) AF: 0.962 AC: 11398 AN: 11846

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3127 AN: 3258

East Asian (EAS) AF: 0.977 AC: 3935 AN: 4028

South Asian (SAS) AF: 0.977 AC: 3317 AN: 3396

European-Finnish (FIN) AF: 0.966 AC: 5981 AN: 6190

Middle Eastern (MID) AF: 0.975 AC: 197 AN: 202

European-Non Finnish (NFE) AF: 0.943 AC: 57904 AN: 61412

Other (OTH) AF: 0.947 AC: 1640 AN: 1732

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58782258;

hg19: chr16-58054465;