1-27886464-C-T

Variant summary

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

The NM_001105556.3(THEMIS2):c.*542C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,278 control chromosomes in the GnomAD database, including 15,019 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 0.44 (14988 hom., cov: 31)
  • Exomes 𝑓: 0.30 (31 hom.)
• Consequence: THEMIS2 NM_001105556.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

Genes affected

THEMIS2 (HGNC:16839): (thymocyte selection associated family member 2) Predicted to be involved in T cell receptor signaling pathway and regulation of B cell activation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS2	NM_001105556.3	c.*542C>T		3_prime_UTR_variant	6/6	ENST00000373921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS2	ENST00000373921.8	c.*542C>T		3_prime_UTR_variant	6/6	5	NM_001105556.3	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66092 AN: 151602 Hom.: 14965 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.299 AC: 167 AN: 558 Hom.: 31 Cov.: 0 AF XY: 0.279 AC XY: 106 AN XY: 380

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.436 AC: 66155 AN: 151720 Hom.: 14988 Cov.: 31 AF XY: 0.432 AC XY: 32008 AN XY: 74112

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.427

Alfa AF: 0.376 Hom.: 10245

Bravo AF: 0.450

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6564; hg19: chr1-28212975;