5-157198268-T-C

Variant names:

• chr5-157198268-T-C
• rs31223
• NM_005546.4:c.139-10621T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005546.4(ITK):​c.139-10621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,086 control chromosomes in the GnomAD database, including 11,681 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 0.39 (11681 hom., cov: 33)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 10 publications found

Genes affected

ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

ITK Gene-Disease associations (from GenCC):

• lymphoproliferative syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• lymphoproliferative syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005546.4. 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
	ITK	NM_005546.4	MANE Select	c.139-10621T>C		intron	N/A	NP_005537.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITK	ENST00000422843.8	TSL:1 MANE Select	c.139-10621T>C		intron	N/A	ENSP00000398655.4
	ITK	ENST00000521769.5	TSL:4	c.-237-10621T>C		intron	N/A	ENSP00000430327.1
	ITK	ENST00000517779.1	TSL:5	n.139-10621T>C		intron	N/A	ENSP00000431054.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59332 AN: 151968 Hom.: 11678 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.390 AC: 59358 AN: 152086 Hom.: 11681 Cov.: 33 AF XY: 0.389 AC XY: 28886 AN XY: 74350

African (AFR) AF: 0.398 AC: 16526 AN: 41482

American (AMR) AF: 0.345 AC: 5274 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2177 AN: 5180

South Asian (SAS) AF: 0.384 AC: 1853 AN: 4822

European-Finnish (FIN) AF: 0.415 AC: 4391 AN: 10572

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26298 AN: 67960

Other (OTH) AF: 0.408 AC: 862 AN: 2112

Alfa AF: 0.383 Hom.: 19508

Bravo AF: 0.386

Asia WGS AF: 0.423 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.026
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: rs31223; hg19: chr5-156625279;