5-150387534-G-T

Variant names:

• chr5-150387534-G-T
• rs1864957
• NM_001371623.1:c.2860-368G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TCOF1 Gene-Disease associations (from GenCC):

• Treacher Collins syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371623.1. 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
	TCOF1	NM_001371623.1	MANE Select	c.2860-368G>T		intron	N/A	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.2860-368G>T		intron	N/A	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.2860-368G>T		intron	N/A	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.2860-368G>T		intron	N/A	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.2860-368G>T		intron	N/A	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000323668.11	TSL:1	c.2629-368G>T		intron	N/A	ENSP00000325223.6	Q13428-2

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

African (AFR) AF: 0.238 AC: 9880 AN: 41484

American (AMR) AF: 0.351 AC: 5369 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2224 AN: 5170

South Asian (SAS) AF: 0.475 AC: 2293 AN: 4824

European-Finnish (FIN) AF: 0.386 AC: 4063 AN: 10524

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29767 AN: 67906

Other (OTH) AF: 0.377 AC: 795 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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