rs1416473

Positions:

• chr1-235399944-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003193.5(TBCE):​c.101-1559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,046 control chromosomes in the GnomAD database, including 42,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (42091 hom., cov: 31)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCE	NM_003193.5	c.101-1559C>T		intron_variant		ENST00000642610.2
TBCE	NM_001079515.3	c.101-1559C>T		intron_variant
TBCE	NM_001287801.2	c.101-1559C>T		intron_variant
TBCE	NM_001287802.2	c.-210-14489C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCE	ENST00000642610.2	c.101-1559C>T		intron_variant			NM_003193.5	P1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111373 AN: 151928 Hom.: 42023 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.733 AC: 111510 AN: 152046 Hom.: 42091 Cov.: 31 AF XY: 0.731 AC XY: 54308 AN XY: 74308

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.741

Alfa AF: 0.535 Hom.: 1142

Bravo AF: 0.745

Asia WGS AF: 0.645 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.37

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: rs1416473; hg19: chr1-235563259; COSMIC: COSV64005526; COSMIC: COSV64005526;