rs411174

chr5-157181989-G-A

Variant summary

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

The NM_005546.4(ITK):c.138+874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,068 control chromosomes in the GnomAD database, including 9,106 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 0.34 (9106 hom., cov: 32)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITK	NM_005546.4	c.138+874G>A		intron_variant		ENST00000422843.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITK	ENST00000422843.8	c.138+874G>A		intron_variant		1	NM_005546.4	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51222 AN: 151950 Hom.: 9088 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.337 AC: 51277 AN: 152068 Hom.: 9106 Cov.: 32 AF XY: 0.333 AC XY: 24766 AN XY: 74334

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.321

Alfa AF: 0.313 Hom.: 13813

Bravo AF: 0.338

Asia WGS AF: 0.265 AC: 919 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.76
Dann	Benign	0.23

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: rs411174; hg19: chr5-156609000;