rs270015

chr6-127772357-T-C

Variant summary

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

The NM_001010923.3(THEMIS):c.1758+40526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,972 control chromosomes in the GnomAD database, including 6,940 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 0.27 (6940 hom., cov: 32)
• Consequence: THEMIS NM_001010923.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

THEMIS (HGNC:21569): (thymocyte selection associated) This gene encodes a protein that plays a regulatory role in both positive and negative T-cell selection during late thymocyte development. The protein functions through T-cell antigen receptor signaling, and is necessary for proper lineage commitment and maturation of T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS	NM_001010923.3	c.1758+40526A>G		intron_variant		ENST00000368248.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS	ENST00000368248.5	c.1758+40526A>G		intron_variant		1	NM_001010923.3	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40818 AN: 151854 Hom.: 6943 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.269 AC: 40811 AN: 151972 Hom.: 6940 Cov.: 32 AF XY: 0.262 AC XY: 19446 AN XY: 74266

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.276

Alfa AF: 0.295 Hom.: 1181

Bravo AF: 0.251

Asia WGS AF: 0.0750 AC: 262 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.4
Dann	Benign	0.77

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: rs270015; hg19: chr6-128093502;