rs112874007

Positions:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024598.4(USB1):​c.*322_*323insCTCTTCCTCTCCTCTCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (14 hom., cov: 0)
  • Exomes 𝑓: 0.0033 (25 hom.)
  • Failed GnomAD Quality Control
• Consequence: USB1 NM_024598.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00129 (159/123114) while in subpopulation EAS AF= 0.0166 (67/4028). AF 95% confidence interval is 0.0134. There are 14 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USB1	NM_024598.4	c.*322_*323insCTCTTCCTCTCCTCTCTCTCT		3_prime_UTR_variant	7/7	ENST00000219281.8	NP_078874.2
USB1	NM_001195302.2	c.*322_*323insCTCTTCCTCTCCTCTCTCTCT		3_prime_UTR_variant	6/6		NP_001182231.1
USB1	NM_001330568.2	c.*322_*323insCTCTTCCTCTCCTCTCTCTCT		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.*322_*323insCTCTTCCTCTCCTCTCTCTCT		3_prime_UTR_variant	7/7	1	NM_024598.4	ENSP00000219281

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 160 AN: 122982 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000338

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.00912

Gnomad FIN AF: 0.000323

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.0000325

Gnomad OTH AF: 0.00409

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00326 AC: 745 AN: 228848 Hom.: 25 Cov.: 0 AF XY: 0.00420 AC XY: 520 AN XY: 123948

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0179

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.0000956

Gnomad4 NFE exome AF: 0.0000920

Gnomad4 OTH exome AF: 0.00296

GnomAD4 genome AF: 0.00129 AC: 159 AN: 123114 Hom.: 14 Cov.: 0 AF XY: 0.00149 AC XY: 87 AN XY: 58554

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.000338

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.000323

Gnomad4 NFE AF: 0.0000325

Gnomad4 OTH AF: 0.00404

ClinVar

Not reported in ClinVar

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;