chr5-150374871-G-C

Position:

• chr5-150374871-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001371623.1(TCOF1):​c.1278+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,610,052 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (14 hom., cov: 34)
  • Exomes 𝑓: 0.0093 (91 hom.)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.136

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-150374871-G-C is Benign according to our data. Variant chr5-150374871-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 209026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00825 (1245/150848) while in subpopulation AMR AF= 0.0169 (257/15208). AF 95% confidence interval is 0.0152. There are 14 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1	c.1278+60G>C		intron_variant		ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2	c.1278+60G>C		intron_variant			NM_001371623.1	ENSP00000493815.1

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1244 AN: 150714 Hom.: 14 Cov.: 34

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00778

Gnomad FIN AF: 0.00450

Gnomad MID AF: 0.0137

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0160

GnomAD4 exome AF: 0.00929 AC: 13562 AN: 1459204 Hom.: 91 Cov.: 33 AF XY: 0.00939 AC XY: 6815 AN XY: 725834

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00743

Gnomad4 ASJ exome AF: 0.0230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00802

Gnomad4 FIN exome AF: 0.00413

Gnomad4 NFE exome AF: 0.00984

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.00825 AC: 1245 AN: 150848 Hom.: 14 Cov.: 34 AF XY: 0.00798 AC XY: 588 AN XY: 73670

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00778

Gnomad4 FIN AF: 0.00450

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0158

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.00820

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Treacher Collins syndrome 1 Benign:1

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	-0.84
CADD	Benign	2.5
DANN	Benign	0.58

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: rs143713714; hg19: chr5-149754434;