chr5-150357905-AGCGGCCC-A

Variant names:

• chr5-150357905-AGCGGCCC-A
• rs151344564
• NM_001371623.1:c.108+62_108+68delGCCCGCG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001371623.1(TCOF1):​c.108+62_108+68delGCCCGCG 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
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 331 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.108+62_108+68delGCCCGCG		intron	N/A	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.108+62_108+68delGCCCGCG		intron	N/A	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.108+62_108+68delGCCCGCG		intron	N/A	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.108+52_108+58delGCGGCCC		intron	N/A	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.108+52_108+58delGCGGCCC		intron	N/A	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000323668.11	TSL:1	c.108+52_108+58delGCGGCCC		intron	N/A	ENSP00000325223.6	Q13428-2

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

GnomAD2 exomes AF: 0.00288 AC: 399 AN: 138534 AF XY: 0.00297

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 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

African (AFR) AF: 0.00 AC: 0 AN: 30508

American (AMR) AF: 0.0000283 AC: 1 AN: 35314

Ashkenazi Jewish (ASJ) AF: 0.00121 AC: 30 AN: 24826

East Asian (EAS) AF: 0.0139 AC: 488 AN: 35198

South Asian (SAS) AF: 0.00113 AC: 89 AN: 78476

European-Finnish (FIN) AF: 0.0177 AC: 788 AN: 44556

Middle Eastern (MID) AF: 0.000229 AC: 1 AN: 4372

European-Non Finnish (NFE) AF: 0.000146 AC: 156 AN: 1067654

Other (OTH) AF: 0.00136 AC: 78 AN: 57152

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

African (AFR) AF: 0.0000530 AC: 2 AN: 37702

American (AMR) AF: 0.000276 AC: 4 AN: 14482

Ashkenazi Jewish (ASJ) AF: 0.00245 AC: 8 AN: 3264

East Asian (EAS) AF: 0.0146 AC: 66 AN: 4530

South Asian (SAS) AF: 0.00136 AC: 6 AN: 4418

European-Finnish (FIN) AF: 0.0196 AC: 201 AN: 10250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.000690 AC: 43 AN: 62302

Other (OTH) AF: 0.000526 AC: 1 AN: 1902

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.000782

Asia WGS AF: 0.00578 AC: 20 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Treacher Collins syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs151344564; hg19: chr5-149737468;