Variant chr5-150357905-AGCGGCCC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001371623.1(TCOF1):c.108+62_108+68del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,517,944 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 14 hom. )

Consequence

TCOF1
NM_001371623.1 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.160

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-150357905-AGCGGCCC-A is Benign according to our data. Variant chr5-150357905-AGCGGCCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 209021.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00237 (331/139888) while in subpopulation EAS AF= 0.0146 (66/4530). AF 95% confidence interval is 0.0117. There are 2 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript	c.108+62_108+68del		intron_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2 linkuse as main transcript	c.108+62_108+68del		intron_variant			NM_001371623.1	P3	Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

330

AN:

139762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000276

Gnomad ASJ

AF:

0.00245

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.00136

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000690

Gnomad OTH

AF:

0.000532

GnomAD3 exomes

AF:

0.00288

AC:

399

AN:

138534

Hom.:

AF XY:

0.00297

AC XY:

222

AN XY:

74810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000823

Gnomad ASJ exome

AF:

0.00123

Gnomad EAS exome

AF:

0.0151

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.000417

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00118

AC:

1631

AN:

1378056

Hom.:

AF XY:

0.00118

AC XY:

802

AN XY:

679970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000283

Gnomad4 ASJ exome

AF:

0.00121

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00237

AC:

331

AN:

139888

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

225

AN XY:

69002

show subpopulations

Gnomad4 AFR

AF:

0.0000530

Gnomad4 AMR

AF:

0.000276

Gnomad4 ASJ

AF:

0.00245

Gnomad4 EAS

AF:

0.0146

Gnomad4 SAS

AF:

0.00136

Gnomad4 FIN

AF:

0.0196

Gnomad4 NFE

AF:

0.000690

Gnomad4 OTH

AF:

0.000526

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.000782

Asia WGS

AF:

0.00578

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Treacher Collins syndrome 1

Benign:1

Likely benign, no assertion criteria provided

not provided

Genetics Laboratories, Oxford Radcliffe Hospitals NHS Trust

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over