rs528897827

Variant names:

• chr5-150372182-TAGTGAGGAGGGATCTGAA-T
• rs528897827
• NM_001371623.1:c.827_844delGATCTGAAAGTGAGGAGG

Your query was ambiguous. Multiple possible variants found:

• chr5-150372182-TAGTGAGGAGGGATCTGAA-T
• chr5-150372182-TAGTGAGGAGGGATCTGAA-TAGTGAGGAGGGATCTGAAAGTGAGGAGGGATCTGAA

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001371623.1(TCOF1):​c.827_844delGATCTGAAAGTGAGGAGG​(p.Gly276_Glu281del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00362 in 1,612,938 control chromosomes in the GnomAD database, including 23 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (22 hom.)
• Consequence: TCOF1 NM_001371623.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.76
• Publications: 0 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001371623.1.
• BP6: Variant 5-150372182-TAGTGAGGAGGGATCTGAA-T is Benign according to our data. Variant chr5-150372182-TAGTGAGGAGGGATCTGAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 431981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00257 (388/151240) while in subpopulation AMR AF = 0.00486 (74/15214). AF 95% confidence interval is 0.00397. There are 1 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 388 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371623.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	NM_001371623.1	MANE Select	c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 27	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 27	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 26	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 27	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 26	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000394269.7	TSL:1	c.827_844delGATCTGAAAGTGAGGAGG	p.Gly276_Glu281del	disruptive_inframe_deletion	Exon 7 of 18	ENSP00000377811.3	Q13428-5

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 388 AN: 151122 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000755

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.00487

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000840

Gnomad FIN AF: 0.00315

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00353

Gnomad OTH AF: 0.00242

GnomAD2 exomes AF: 0.00196 AC: 488 AN: 248872 AF XY: 0.00203

Gnomad AFR exome AF: 0.000260

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00140

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00373 AC: 5458 AN: 1461698 Hom.: 22 AF XY: 0.00358 AC XY: 2605 AN XY: 727146

African (AFR) AF: 0.000657 AC: 22 AN: 33476

American (AMR) AF: 0.00148 AC: 66 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00154 AC: 133 AN: 86248

European-Finnish (FIN) AF: 0.00155 AC: 83 AN: 53412

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5740

European-Non Finnish (NFE) AF: 0.00446 AC: 4958 AN: 1111900

Other (OTH) AF: 0.00313 AC: 189 AN: 60380

GnomAD4 genome AF: 0.00257 AC: 388 AN: 151240 Hom.: 1 Cov.: 33 AF XY: 0.00259 AC XY: 191 AN XY: 73854

African (AFR) AF: 0.000753 AC: 31 AN: 41164

American (AMR) AF: 0.00486 AC: 74 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.000841 AC: 4 AN: 4758

European-Finnish (FIN) AF: 0.00315 AC: 33 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00353 AC: 239 AN: 67758

Other (OTH) AF: 0.00239 AC: 5 AN: 2092

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00271

EpiCase AF: 0.00316

EpiControl AF: 0.00350

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)
-	-	1	TCOF1-related disorder (1)
-	-	1	Treacher Collins syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=193/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs528897827; hg19: chr5-149751745;