17-44207100-ATTTTT-ATTTT

Variant names:

• chr17-44207100-AT-A
• rs374363130
• NM_014233.4:c.*141delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014233.4(UBTF):​c.*141delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 136,616 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (45 hom., cov: 29)
  • Exomes 𝑓: 0.39 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140
• Publications: 1 publications found

Genes affected

UBTF (HGNC:12511): (upstream binding transcription factor) This gene encodes a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions. The encoded protein may also play important roles in chromatin remodeling and pre-rRNA processing, and its activity is regulated by both phosphorylation and acetylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3, 11 and X and the long arm of chromosome 11. [provided by RefSeq, Aug 2011]

ATXN7L3-AS1 (HGNC:55298): (ATXN7L3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-44207100-AT-A is Benign according to our data. Variant chr17-44207100-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1258422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0255 (3483/136616) while in subpopulation AFR AF = 0.0489 (1822/37246). AF 95% confidence interval is 0.047. There are 45 homozygotes in GnomAd4. There are 1752 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3483 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014233.4. 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
	UBTF	NM_014233.4	MANE Select	c.*141delA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*141delA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*141delA		3_prime_UTR	Exon 20 of 20	NP_001070152.1	P17480-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTF	ENST00000436088.6	TSL:2 MANE Select	c.*141delA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*141delA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*141delA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3474 AN: 136622 Hom.: 45 Cov.: 29

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.00504

Gnomad SAS AF: 0.00347

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0276

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0225

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.389 AC: 230016 AN: 590750 Hom.: 6 Cov.: 0 AF XY: 0.393 AC XY: 118450 AN XY: 301566

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.406 AC: 5909 AN: 14556

American (AMR) AF: 0.441 AC: 7432 AN: 16838

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 5536 AN: 12798

East Asian (EAS) AF: 0.448 AC: 11731 AN: 26172

South Asian (SAS) AF: 0.426 AC: 18192 AN: 42742

European-Finnish (FIN) AF: 0.441 AC: 10820 AN: 24550

Middle Eastern (MID) AF: 0.412 AC: 834 AN: 2022

European-Non Finnish (NFE) AF: 0.374 AC: 157869 AN: 422446

Other (OTH) AF: 0.408 AC: 11693 AN: 28626

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0255 AC: 3483 AN: 136616 Hom.: 45 Cov.: 29 AF XY: 0.0265 AC XY: 1752 AN XY: 66088

African (AFR) AF: 0.0489 AC: 1822 AN: 37246

American (AMR) AF: 0.0150 AC: 206 AN: 13690

Ashkenazi Jewish (ASJ) AF: 0.0261 AC: 85 AN: 3258

East Asian (EAS) AF: 0.00506 AC: 24 AN: 4740

South Asian (SAS) AF: 0.00395 AC: 17 AN: 4304

European-Finnish (FIN) AF: 0.0532 AC: 424 AN: 7976

Middle Eastern (MID) AF: 0.0301 AC: 8 AN: 266

European-Non Finnish (NFE) AF: 0.0137 AC: 854 AN: 62440

Other (OTH) AF: 0.0229 AC: 42 AN: 1836

Alfa AF: 0.00252 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs374363130; hg19: chr17-42284468; COSMIC: COSV57184612; COSMIC: COSV57184612;