5-150387534-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371623.1(TCOF1):c.2860-368G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,960 control chromosomes in the GnomAD database, including 11,241 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11241 hom., cov: 33)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1	c.2860-368G>T		intron_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2	c.2860-368G>T		intron_variant			NM_001371623.1	P3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56664 AN: 151842 Hom.: 11243 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56668 AN: 151960 Hom.: 11241 Cov.: 33 AF XY: 0.374 AC XY: 27746 AN XY: 74270

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.377

Alfa AF: 0.253 Hom.: 602

Bravo AF: 0.361

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.5
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs1864957; hg19: chr5-149767097; COSMIC: COSV60347002; COSMIC: COSV60347002;