Variant chr5-150374871-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001371623.1(TCOF1):c.1278+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,610,052 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0083 ( 14 hom., cov: 34)

Exomes 𝑓: 0.0093 ( 91 hom. )

Consequence

TCOF1
NM_001371623.1 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.136

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-150374871-G-C is Benign according to our data. Variant chr5-150374871-G-C is described in ClinVar as [Benign]. Clinvar id is 209026.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00825 (1245/150848) while in subpopulation AMR AF= 0.0169 (257/15208). AF 95% confidence interval is 0.0152. There are 14 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript	c.1278+60G>C		intron_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2 linkuse as main transcript	c.1278+60G>C		intron_variant			NM_001371623.1	P3	Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1244

AN:

150714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00778

Gnomad FIN

AF:

0.00450

Gnomad MID

AF:

0.0137

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0160

GnomAD4 exome

AF:

0.00929

AC:

13562

AN:

1459204

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

6815

AN XY:

725834

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00743

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00802

Gnomad4 FIN exome

AF:

0.00413

Gnomad4 NFE exome

AF:

0.00984

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00825

AC:

1245

AN:

150848

Hom.:

Cov.:

AF XY:

0.00798

AC XY:

588

AN XY:

73670

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00778

Gnomad4 FIN

AF:

0.00450

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0158

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00820

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Treacher Collins syndrome 1

Benign:1

Benign, no assertion criteria provided

not provided

Genetics Laboratories, Oxford Radcliffe Hospitals NHS Trust

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

DANN

Benign

0.58

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

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