rs2254535

Positions:

• chr10-70778117-C-T

Variant summary

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

The NM_001318241.2(TBATA):​c.507+440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,166 control chromosomes in the GnomAD database, including 59,818 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 0.89 (59818 hom., cov: 31)
• Consequence: TBATA NM_001318241.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

Genes affected

TBATA (HGNC:23511): (thymus, brain and testes associated) This gene encodes a protein that regulates thymic epithelial cell proliferation and thymus size. It has been identified as a ligand for the class I human leukocyte antigen (HLA-I) in thymus. Studies of the orthologous mouse protein suggest that it may also play a role in spermatid differentiation, as well as in neuronal morphogenesis and synaptic plasticity. Polymorphisms in this gene are associated with susceptibility for multiple sclerosis (MS). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBATA	NM_001318241.2	c.507+440G>A		intron_variant		ENST00000456372.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBATA	ENST00000456372.4	c.507+440G>A		intron_variant		1	NM_001318241.2	A2

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134605 AN: 152048 Hom.: 59789 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.885 AC: 134684 AN: 152166 Hom.: 59818 Cov.: 31 AF XY: 0.882 AC XY: 65637 AN XY: 74398

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.878

Alfa AF: 0.920 Hom.: 87748

Bravo AF: 0.884

Asia WGS AF: 0.822 AC: 2862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.74

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: rs2254535; hg19: chr10-72537873;