5-150357905-AGCGGCCC-A

Position:

• chr5-150357905-AGCGGCCC-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001371623.1(TCOF1):​c.108+62_108+68del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,517,944 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (14 hom.)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.160

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 -9 ACMG points.

• BP6: Variant 5-150357905-AGCGGCCC-A is Benign according to our data. Variant chr5-150357905-AGCGGCCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 209021.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00237 (331/139888) while in subpopulation EAS AF= 0.0146 (66/4530). AF 95% confidence interval is 0.0117. There are 2 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1	c.108+62_108+68del		intron_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2	c.108+62_108+68del		intron_variant			NM_001371623.1	P3

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 330 AN: 139762 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000276

Gnomad ASJ AF: 0.00245

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000690

Gnomad OTH AF: 0.000532

GnomAD3 exomes AF: 0.00288 AC: 399 AN: 138534 Hom.: 2 AF XY: 0.00297 AC XY: 222 AN XY: 74810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000823

Gnomad ASJ exome AF: 0.00123

Gnomad EAS exome AF: 0.0151

Gnomad SAS exome AF: 0.00122

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.000417

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00118 AC: 1631 AN: 1378056 Hom.: 14 AF XY: 0.00118 AC XY: 802 AN XY: 679970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000283

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.00113

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00237 AC: 331 AN: 139888 Hom.: 2 Cov.: 32 AF XY: 0.00326 AC XY: 225 AN XY: 69002

Gnomad4 AFR AF: 0.0000530

Gnomad4 AMR AF: 0.000276

Gnomad4 ASJ AF: 0.00245

Gnomad4 EAS AF: 0.0146

Gnomad4 SAS AF: 0.00136

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.000690

Gnomad4 OTH AF: 0.000526

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.000782

Asia WGS AF: 0.00578 AC: 20 AN: 3474

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs151344564; hg19: chr5-149737468;