rs367153

Variant names:

• chr5-157183835-C-T
• rs367153
• NM_005546.4:c.138+2720C>T

Variant summary

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

The NM_005546.4(ITK):​c.138+2720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,188 control chromosomes in the GnomAD database, including 878 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 0.099 (878 hom., cov: 32)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITK	NM_005546.4	c.138+2720C>T		intron_variant	Intron 1 of 16	ENST00000422843.8	NP_005537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITK	ENST00000422843.8	c.138+2720C>T		intron_variant	Intron 1 of 16	1	NM_005546.4	ENSP00000398655.4

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15041 AN: 152070 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0988 AC: 15040 AN: 152188 Hom.: 878 Cov.: 32 AF XY: 0.0942 AC XY: 7009 AN XY: 74394

African (AFR) AF: 0.0590 AC: 2449 AN: 41506

American (AMR) AF: 0.0979 AC: 1496 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3472

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5192

South Asian (SAS) AF: 0.0556 AC: 268 AN: 4824

European-Finnish (FIN) AF: 0.0803 AC: 850 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9176 AN: 68006

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.111 Hom.: 381

Bravo AF: 0.0987

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.57
PhyloP100		-0.40
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: rs367153; hg19: chr5-156610846;