rs30117

Variant names:

• chr5-157237968-C-A
• rs30117
• NM_005546.4:c.769-141C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-157237968-C-A
• chr5-157237968-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005546.4(ITK):​c.769-141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITK	NM_005546.4	c.769-141C>A		intron_variant	Intron 8 of 16	ENST00000422843.8	NP_005537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITK	ENST00000422843.8	c.769-141C>A		intron_variant	Intron 8 of 16	1	NM_005546.4	ENSP00000398655.4
ITK	ENST00000519402.5	n.904-141C>A		intron_variant	Intron 8 of 15	2
ITK	ENST00000519759.1	n.388-141C>A		intron_variant	Intron 3 of 4	4
ITK	ENST00000696962.1	n.769-141C>A		intron_variant	Intron 8 of 15			ENSP00000513001.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 540722 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 291666

African (AFR) AF: 0.00 AC: 0 AN: 15222

American (AMR) AF: 0.00 AC: 0 AN: 33890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19162

East Asian (EAS) AF: 0.00 AC: 0 AN: 31404

South Asian (SAS) AF: 0.00 AC: 0 AN: 61516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 306630

Other (OTH) AF: 0.00 AC: 0 AN: 29316

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.025
DANN	Benign	0.58
PhyloP100		-0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs30117; hg19: chr5-156664978;