1-27884873-G-A

Position:

• chr1-27884873-G-A

Variant summary

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

The NM_001105556.3(THEMIS2):​c.1720-422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 169,412 control chromosomes in the GnomAD database, including 12,601 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 0.38 (11256 hom., cov: 32)
  • Exomes 𝑓: 0.39 (1345 hom.)
• Consequence: THEMIS2 NM_001105556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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]

THEMIS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEMIS2	NM_001105556.3	c.1720-422G>A		intron_variant		ENST00000373921.8	NP_001099026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEMIS2	ENST00000373921.8	c.1720-422G>A		intron_variant		5	NM_001105556.3	ENSP00000363031.3

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58127 AN: 151920 Hom.: 11241 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.390 AC: 6781 AN: 17374 Hom.: 1345 Cov.: 0 AF XY: 0.382 AC XY: 3707 AN XY: 9698

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.383 AC: 58176 AN: 152038 Hom.: 11256 Cov.: 32 AF XY: 0.379 AC XY: 28191 AN XY: 74326

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.379

Alfa AF: 0.370 Hom.: 6026

Bravo AF: 0.393

Asia WGS AF: 0.339 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.63

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: rs2236074; hg19: chr1-28211384;