rs12048235

Variant names:

• chr1-27879373-G-A
• rs12048235
• NM_001105556.3:c.236-271G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-27879373-G-A
• chr1-27879373-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THEMIS2	NM_001105556.3	c.236-271G>A		intron_variant	Intron 2 of 5	ENST00000373921.8	NP_001099026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THEMIS2	ENST00000373921.8	c.236-271G>A		intron_variant	Intron 2 of 5	5	NM_001105556.3	ENSP00000363031.3

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

African (AFR) AF: 0.101 AC: 4202 AN: 41450

American (AMR) AF: 0.282 AC: 4267 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1204 AN: 3448

East Asian (EAS) AF: 0.399 AC: 2058 AN: 5152

South Asian (SAS) AF: 0.329 AC: 1576 AN: 4794

European-Finnish (FIN) AF: 0.369 AC: 3884 AN: 10538

Middle Eastern (MID) AF: 0.414 AC: 120 AN: 290

European-Non Finnish (NFE) AF: 0.358 AC: 24245 AN: 67688

Other (OTH) AF: 0.299 AC: 627 AN: 2094

Alfa AF: 0.316 Hom.: 3493

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
PhyloP100		-0.17
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12048235; hg19: chr1-28205884;