rs12048235

chr1-27879373-G-Achr1-27879373-G-C

Variant summary

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

The NM_001105556.3(THEMIS2):c.236-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,522 control chromosomes in the GnomAD database, including 7,009 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 0.28 (7009 hom., cov: 30)
• Consequence: THEMIS2 NM_001105556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS2	NM_001105556.3	c.236-271G>A		intron_variant		ENST00000373921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS2	ENST00000373921.8	c.236-271G>A		intron_variant		5	NM_001105556.3	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42649 AN: 151402 Hom.: 7011 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.281 AC: 42643 AN: 151522 Hom.: 7009 Cov.: 30 AF XY: 0.282 AC XY: 20881 AN XY: 74050

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.299

Alfa AF: 0.315 Hom.: 2132

Bravo AF: 0.271

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.64
Dann	Benign	0.46

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: rs12048235; hg19: chr1-28205884;