5-150398801-G-C

Position:

• chr5-150398801-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001371623.1(TCOF1):​c.4444-221G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,124 control chromosomes in the GnomAD database, including 23,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (23943 hom., cov: 34)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-150398801-G-C is Benign according to our data. Variant chr5-150398801-G-C is described in ClinVar as [Benign]. Clinvar id is 1280453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1	c.4444-221G>C		intron_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2	c.4444-221G>C		intron_variant			NM_001371623.1	P3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84960 AN: 152004 Hom.: 23931 Cov.: 34

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 85016 AN: 152124 Hom.: 23943 Cov.: 34 AF XY: 0.556 AC XY: 41340 AN XY: 74352

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.544

Alfa AF: 0.469 Hom.: 1296

Bravo AF: 0.550

Asia WGS AF: 0.507 AC: 1762 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.75
DANN	Benign	0.46

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: rs2569062; hg19: chr5-149778364; COSMIC: COSV50532351; COSMIC: COSV50532351;