NM_001105556.3:c.1720-403A>G

Variant names:

• chr1-27884892-A-G
• rs1467465
• NM_001105556.3:c.1720-403A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105556.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEMIS2	NM_001105556.3	MANE Select	c.1720-403A>G		intron	N/A	NP_001099026.1
	THEMIS2	NM_001286113.2		c.1333-403A>G		intron	N/A	NP_001273042.1
	THEMIS2	NM_001286115.2		c.1132-403A>G		intron	N/A	NP_001273044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEMIS2	ENST00000373921.8	TSL:5 MANE Select	c.1720-403A>G		intron	N/A	ENSP00000363031.3
	THEMIS2	ENST00000456990.1	TSL:1	c.961-403A>G		intron	N/A	ENSP00000398049.1
	THEMIS2	ENST00000373925.5	TSL:1	c.647-403A>G		intron	N/A	ENSP00000363035.1

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

African (AFR) AF: 0.507 AC: 70 AN: 138

American (AMR) AF: 0.743 AC: 721 AN: 970

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 195 AN: 262

East Asian (EAS) AF: 0.657 AC: 218 AN: 332

South Asian (SAS) AF: 0.690 AC: 2826 AN: 4096

European-Finnish (FIN) AF: 0.592 AC: 411 AN: 694

Middle Eastern (MID) AF: 0.804 AC: 45 AN: 56

European-Non Finnish (NFE) AF: 0.625 AC: 6385 AN: 10214

Other (OTH) AF: 0.674 AC: 550 AN: 816

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

African (AFR) AF: 0.483 AC: 20025 AN: 41452

American (AMR) AF: 0.714 AC: 10921 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3470

East Asian (EAS) AF: 0.661 AC: 3419 AN: 5176

South Asian (SAS) AF: 0.691 AC: 3333 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6214 AN: 10578

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44128 AN: 67974

Other (OTH) AF: 0.639 AC: 1348 AN: 2108

Alfa AF: 0.655 Hom.: 54992

Bravo AF: 0.620

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.60
PhyloP100		-1.8
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: rs1467465; hg19: chr1-28211403;