rs2254535

Variant names:

• chr10-70778117-C-T
• rs2254535
• NM_001318241.2:c.507+440G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000456372.4(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 ENST00000456372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBATA	NM_001318241.2	MANE Select	c.507+440G>A		intron	N/A	NP_001305170.1
	TBATA	NM_001318242.2		c.507+440G>A		intron	N/A	NP_001305171.1
	TBATA	NM_152710.4		c.507+440G>A		intron	N/A	NP_689923.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBATA	ENST00000456372.4	TSL:1 MANE Select	c.507+440G>A		intron	N/A	ENSP00000400224.3
	TBATA	ENST00000299290.5	TSL:1	c.507+440G>A		intron	N/A	ENSP00000299290.1
	TBATA	ENST00000692183.1		c.507+440G>A		intron	N/A	ENSP00000509602.1

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

African (AFR) AF: 0.816 AC: 33852 AN: 41500

American (AMR) AF: 0.909 AC: 13908 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3045 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4154 AN: 5154

South Asian (SAS) AF: 0.883 AC: 4251 AN: 4812

European-Finnish (FIN) AF: 0.884 AC: 9357 AN: 10590

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63112 AN: 68016

Other (OTH) AF: 0.878 AC: 1857 AN: 2114

Alfa AF: 0.916 Hom.: 109486

Bravo AF: 0.884

Asia WGS AF: 0.822 AC: 2862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.74
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2254535; hg19: chr10-72537873;