chr5-150357658-T-G

Variant names:

• chr5-150357658-T-G
• rs4565199
• ENST00000377797.7:c.-89T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000930542.1(TCOF1):​c.-89T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,236,910 control chromosomes in the GnomAD database, including 614,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (75833 hom., cov: 32)
  • Exomes 𝑓: 1.0 (538729 hom.)
• Consequence: TCOF1 ENST00000930542.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.696
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae)
• Treacher-Collins syndrome

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

LOC105378226 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-150357658-T-G is Benign according to our data. Variant chr5-150357658-T-G is described in ClinVar as Benign. ClinVar VariationId is 1258191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000930542.1. 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.-89T>G		upstream_gene	N/A	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.-89T>G		upstream_gene	N/A	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.-89T>G		upstream_gene	N/A	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000377797.7	TSL:5	c.-89T>G		5_prime_UTR	Exon 1 of 27	ENSP00000367028.4	Q13428-1
	TCOF1	ENST00000930542.1		c.-89T>G		5_prime_UTR	Exon 1 of 26	ENSP00000600601.1
	TCOF1	ENST00000650162.1		c.-89T>G		5_prime_UTR	Exon 1 of 23	ENSP00000497075.1	A0A3B3IS06

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151854 AN: 152160 Hom.: 75774 Cov.: 32

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.998

GnomAD4 exome AF: 0.997 AC: 1081040 AN: 1084632 Hom.: 538729 Cov.: 14 AF XY: 0.997 AC XY: 544095 AN XY: 545890

African (AFR) AF: 0.999 AC: 24447 AN: 24462

American (AMR) AF: 0.999 AC: 34269 AN: 34296

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 22486 AN: 22556

East Asian (EAS) AF: 1.00 AC: 33314 AN: 33314

South Asian (SAS) AF: 1.00 AC: 71987 AN: 71988

European-Finnish (FIN) AF: 1.00 AC: 39074 AN: 39092

Middle Eastern (MID) AF: 1.00 AC: 3464 AN: 3464

European-Non Finnish (NFE) AF: 0.996 AC: 804798 AN: 808168

Other (OTH) AF: 0.998 AC: 47201 AN: 47292

GnomAD4 genome AF: 0.998 AC: 151972 AN: 152278 Hom.: 75833 Cov.: 32 AF XY: 0.998 AC XY: 74333 AN XY: 74466

African (AFR) AF: 0.999 AC: 41532 AN: 41572

American (AMR) AF: 1.00 AC: 15309 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5138 AN: 5138

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10611 AN: 10614

Middle Eastern (MID) AF: 1.00 AC: 292 AN: 292

European-Non Finnish (NFE) AF: 0.996 AC: 67779 AN: 68024

Other (OTH) AF: 0.998 AC: 2108 AN: 2112

Alfa AF: 0.997 Hom.: 9202

Bravo AF: 0.998

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		0.70
PromoterAI		0.099	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4565199; hg19: chr5-149737221;