rs1467465

chr1-27884892-A-G

Variant summary

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

The NM_001105556.3(THEMIS2):c.1720-403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 169,658 control chromosomes in the GnomAD database, including 32,910 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 0.61 (29079 hom., cov: 32)
  • Exomes 𝑓: 0.65 (3831 hom.)
• Consequence: THEMIS2 NM_001105556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS2	NM_001105556.3	c.1720-403A>G		intron_variant		ENST00000373921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS2	ENST00000373921.8	c.1720-403A>G		intron_variant		5	NM_001105556.3	P1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92938 AN: 151962 Hom.: 29076 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.650 AC: 11421 AN: 17578 Hom.: 3831 Cov.: 0 AF XY: 0.657 AC XY: 6452 AN XY: 9826

Gnomad4 AFR exome AF: 0.507

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.657

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.611 AC: 92977 AN: 152080 Hom.: 29079 Cov.: 32 AF XY: 0.611 AC XY: 45402 AN XY: 74340

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.639

Alfa AF: 0.660 Hom.: 43959

Bravo AF: 0.620

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.10
Dann	Benign	0.60

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: rs1467465; hg19: chr1-28211403;