rs151182547

Positions:

• chr5-150379502-TCTCTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001371623.1(TCOF1):​c.2659-24_2659-20del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,614,046 control chromosomes in the GnomAD database, including 5,130 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.057 (323 hom., cov: 31)
  • Exomes 𝑓: 0.078 (4807 hom.)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834

Genes affected

TCOF1 (HGNC:11654): (treacle ribosome biogenesis factor 1) This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-150379502-TCTCTC-T is Benign according to our data. Variant chr5-150379502-TCTCTC-T is described in ClinVar as [Benign]. Clinvar id is 257550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1	c.2659-24_2659-20del		intron_variant		ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2	c.2659-24_2659-20del		intron_variant			NM_001371623.1	ENSP00000493815	P3

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8676 AN: 152084 Hom.: 320 Cov.: 31

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0474

GnomAD3 exomes AF: 0.0689 AC: 17284 AN: 250984 Hom.: 760 AF XY: 0.0709 AC XY: 9624 AN XY: 135740

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0341

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.0926

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0755

Gnomad OTH exome AF: 0.0597

GnomAD4 exome AF: 0.0778 AC: 113756 AN: 1461844 Hom.: 4807 AF XY: 0.0782 AC XY: 56878 AN XY: 727230

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.0806

Gnomad4 SAS exome AF: 0.0927

Gnomad4 FIN exome AF: 0.0713

Gnomad4 NFE exome AF: 0.0824

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.0571 AC: 8685 AN: 152202 Hom.: 323 Cov.: 31 AF XY: 0.0572 AC XY: 4254 AN XY: 74402

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.0701

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0647 Hom.: 63

Bravo AF: 0.0515

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		5.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs151182547; hg19: chr5-149759065;