5-150357688-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.15

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]

ACMG classification

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 GnomAd at 234 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2			upstream_gene_variant			NM_001371623.1	P3

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152144 Hom.: 0 Cov.: 32

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.: 7 Cov.: 21 AF XY: 0.00239 AC XY: 1571 AN XY: 656574

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.: 0 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74464

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.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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
BayesDel_noAF	Benign	-0.46
Cadd	Benign	19
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

Other links and lift over

dbSNP: rs151344563; hg19: chr5-149737251;