rs2071238

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001371623.1(TCOF1):c.1578C>T(p.Pro526Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,736 control chromosomes in the GnomAD database, including 20,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2494 hom., cov: 34)

Exomes 𝑓: 0.15 ( 18134 hom. )

Consequence

TCOF1
NM_001371623.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.299

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

Treacher Collins syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Treacher-Collins syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

TCOF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-150375428-C-T is Benign according to our data. Variant chr5-150375428-C-T is described in ClinVar as Benign. ClinVar VariationId is 130562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.299 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.1578C>T	p.Pro526Pro	synonymous_variant	Exon 11 of 27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2 link	c.1578C>T	p.Pro526Pro	synonymous_variant	Exon 11 of 27		NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26247

AN:

151590

Hom.:

2489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0563

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.142

AC:

35687

AN:

250908

AF XY:

0.141

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.0836

Gnomad ASJ exome

AF:

0.0619

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.154

AC:

224991

AN:

1461032

Hom.:

18134

Cov.:

AF XY:

0.153

AC XY:

111326

AN XY:

726732

show subpopulations

African (AFR)

AF:

0.254

AC:

8487

AN:

33454

American (AMR)

AF:

0.0866

AC:

3868

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0600

AC:

1567

AN:

26126

East Asian (EAS)

AF:

0.0898

AC:

3566

AN:

39690

South Asian (SAS)

AF:

0.139

AC:

11965

AN:

86216

European-Finnish (FIN)

AF:

0.138

AC:

7342

AN:

53392

Middle Eastern (MID)

AF:

0.106

AC:

583

AN:

5482

European-Non Finnish (NFE)

AF:

0.161

AC:

178423

AN:

1111648

Other (OTH)

AF:

0.152

AC:

9190

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12440

24880

37321

49761

62201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6366

12732

19098

25464

31830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.173

AC:

26295

AN:

151704

Hom.:

2494

Cov.:

AF XY:

0.171

AC XY:

12643

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.250

AC:

10363

AN:

41408

American (AMR)

AF:

0.118

AC:

1800

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0563

AC:

195

AN:

3466

East Asian (EAS)

AF:

0.130

AC:

656

AN:

5062

South Asian (SAS)

AF:

0.128

AC:

615

AN:

4790

European-Finnish (FIN)

AF:

0.137

AC:

1451

AN:

10578

Middle Eastern (MID)

AF:

0.112

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.159

AC:

10754

AN:

67826

Other (OTH)

AF:

0.159

AC:

335

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1090

2180

3271

4361

5451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

941

Bravo

AF:

0.174

Asia WGS

AF:

0.157

AC:

543

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Treacher Collins syndrome 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.9

(source)

DANN

Benign

0.43

PhyloP100

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over