rs2255796

Positions:

• chr5-150371783-G-A
• chr5-150371783-G-T

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.640-223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,018 control chromosomes in the GnomAD database, including 12,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12357 hom., cov: 32)
• Consequence: TCOF1 NM_001371623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.706

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=-0.88).
• BP6: Variant 5-150371783-G-A is Benign according to our data. Variant chr5-150371783-G-A is described in ClinVar as [Benign]. Clinvar id is 1274744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1	c.640-223G>A		intron_variant		ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2	c.640-223G>A		intron_variant			NM_001371623.1	ENSP00000493815	P3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60741 AN: 151898 Hom.: 12360 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.400 AC: 60762 AN: 152018 Hom.: 12357 Cov.: 32 AF XY: 0.399 AC XY: 29646 AN XY: 74296

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.398

Alfa AF: 0.328 Hom.: 1174

Bravo AF: 0.393

Asia WGS AF: 0.380 AC: 1320 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	-0.88
CADD	Benign	0.59
DANN	Benign	0.70

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: rs2255796; hg19: chr5-149751346; COSMIC: COSV60346964; COSMIC: COSV60346964;