Variant rs2071239 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001371623.1(TCOF1):c.1842A>G(p.Ser614Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,614,034 control chromosomes in the GnomAD database, including 20,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2638 hom., cov: 34)

Exomes 𝑓: 0.15 ( 18295 hom. )

Consequence

TCOF1
NM_001371623.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.12

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:

TCOF1 (HGNC:):

TCOF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-150375858-A-G is Benign according to our data. Variant chr5-150375858-A-G is described in ClinVar as [Benign]. Clinvar id is 130565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150375858-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript	c.1842A>G	p.Ser614Ser	synonymous_variant	12/27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2 linkuse as main transcript	c.1842A>G	p.Ser614Ser	synonymous_variant	12/27		NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26894

AN:

152064

Hom.:

2633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.143

AC:

36033

AN:

251288

Hom.:

2949

AF XY:

0.142

AC XY:

19338

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.0844

Gnomad ASJ exome

AF:

0.0619

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.155

AC:

225866

AN:

1461852

Hom.:

18295

Cov.:

AF XY:

0.154

AC XY:

111754

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.0874

Gnomad4 ASJ exome

AF:

0.0600

Gnomad4 EAS exome

AF:

0.0905

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.177

AC:

26941

AN:

152182

Hom.:

2638

Cov.:

AF XY:

0.174

AC XY:

12949

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0562

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.155

Hom.:

4565

Bravo

AF:

0.179

Asia WGS

AF:

0.156

AC:

540

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Treacher Collins syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.23

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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