rs452223

chr5-157184482-T-C

Variant summary

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

The NM_005546.4(ITK):c.138+3367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,094 control chromosomes in the GnomAD database, including 43,106 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 0.75 (43106 hom., cov: 31)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITK	NM_005546.4	c.138+3367T>C		intron_variant		ENST00000422843.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITK	ENST00000422843.8	c.138+3367T>C		intron_variant		1	NM_005546.4	P1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113869 AN: 151976 Hom.: 43057 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.749 AC: 113976 AN: 152094 Hom.: 43106 Cov.: 31 AF XY: 0.743 AC XY: 55262 AN XY: 74336

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.745

Alfa AF: 0.723 Hom.: 21997

Bravo AF: 0.759

Asia WGS AF: 0.669 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.4
Dann	Benign	0.33

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: rs452223; hg19: chr5-156611493;