chr5-150379502-TCTCTC-T

Variant names:

• chr5-150379502-TCTCTC-T
• rs151182547
• NM_001371623.1:c.2659-24_2659-20delCTCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001371623.1(TCOF1):​c.2659-24_2659-20delCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,614,046 control chromosomes in the GnomAD database, including 5,130 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.057 (323 hom., cov: 31)
  • Exomes 𝑓: 0.078 (4807 hom.)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-150379502-TCTCTC-T is Benign according to our data. Variant chr5-150379502-TCTCTC-T is described in ClinVar as Benign. ClinVar VariationId is 257550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	NM_001371623.1	MANE Select	c.2659-24_2659-20delCTCTC		intron	N/A	NP_001358552.1
	TCOF1	NM_001135243.2		c.2659-24_2659-20delCTCTC		intron	N/A	NP_001128715.1
	TCOF1	NM_001135244.2		c.2659-24_2659-20delCTCTC		intron	N/A	NP_001128716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.2659-29_2659-25delCTCTC		intron	N/A	ENSP00000493815.1
	TCOF1	ENST00000504761.6	TSL:1	c.2659-29_2659-25delCTCTC		intron	N/A	ENSP00000421655.2
	TCOF1	ENST00000323668.11	TSL:1	c.2428-29_2428-25delCTCTC		intron	N/A	ENSP00000325223.6

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8676 AN: 152084 Hom.: 320 Cov.: 31

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0474

GnomAD2 exomes AF: 0.0689 AC: 17284 AN: 250984 AF XY: 0.0709

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0341

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0755

Gnomad OTH exome AF: 0.0597

GnomAD4 exome AF: 0.0778 AC: 113756 AN: 1461844 Hom.: 4807 AF XY: 0.0782 AC XY: 56878 AN XY: 727230

African (AFR) AF: 0.0119 AC: 400 AN: 33478

American (AMR) AF: 0.0350 AC: 1567 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 649 AN: 26136

East Asian (EAS) AF: 0.0806 AC: 3201 AN: 39698

South Asian (SAS) AF: 0.0927 AC: 7997 AN: 86250

European-Finnish (FIN) AF: 0.0713 AC: 3809 AN: 53406

Middle Eastern (MID) AF: 0.0291 AC: 168 AN: 5768

European-Non Finnish (NFE) AF: 0.0824 AC: 91640 AN: 1111994

Other (OTH) AF: 0.0716 AC: 4325 AN: 60394

GnomAD4 genome AF: 0.0571 AC: 8685 AN: 152202 Hom.: 323 Cov.: 31 AF XY: 0.0572 AC XY: 4254 AN XY: 74402

African (AFR) AF: 0.0141 AC: 587 AN: 41548

American (AMR) AF: 0.0408 AC: 624 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5172

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4828

European-Finnish (FIN) AF: 0.0701 AC: 743 AN: 10592

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0815 AC: 5541 AN: 67976

Other (OTH) AF: 0.0512 AC: 108 AN: 2110

Alfa AF: 0.0647 Hom.: 63

Bravo AF: 0.0515

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs151182547; hg19: chr5-149759065;