Variant chr5-150357688-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The ENST00000323668.11(TCOF1):c.-59G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,476,980 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

TCOF1
ENST00000323668.11 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.15

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 5-150357688-G-A is Benign according to our data. Variant chr5-150357688-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 209019.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150357688-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00154 (234/152262) while in subpopulation AMR AF= 0.00366 (56/15300). AF 95% confidence interval is 0.00289. There are 0 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript			upstream_gene_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2 linkuse as main transcript			upstream_gene_variant			NM_001371623.1	P3	Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.00236

AC:

3127

AN:

1324718

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1571

AN XY:

656574

show subpopulations

Gnomad4 AFR exome

AF:

0.000535

Gnomad4 AMR exome

AF:

0.00588

Gnomad4 ASJ exome

AF:

0.000407

Gnomad4 EAS exome

AF:

0.0000284

Gnomad4 SAS exome

AF:

0.00388

Gnomad4 FIN exome

AF:

0.000699

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152262

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00172

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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