5-157197389-A-G

Variant names:

• chr5-157197389-A-G
• rs25855
• NM_005546.4:c.139-11500A>G

Variant summary

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

The NM_005546.4(ITK):​c.139-11500A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,206 control chromosomes in the GnomAD database, including 54,073 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 0.84 (54073 hom., cov: 32)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 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.139-11500A>G		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.139-11500A>G		intron	N/A	ENSP00000398655.4
	ITK	ENST00000521769.5	TSL:4	c.-237-11500A>G		intron	N/A	ENSP00000430327.1
	ITK	ENST00000517779.1	TSL:5	n.139-11500A>G		intron	N/A	ENSP00000431054.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127536 AN: 152088 Hom.: 54020 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.839 AC: 127647 AN: 152206 Hom.: 54073 Cov.: 32 AF XY: 0.832 AC XY: 61930 AN XY: 74394

African (AFR) AF: 0.962 AC: 39990 AN: 41560

American (AMR) AF: 0.784 AC: 11987 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2583 AN: 3472

East Asian (EAS) AF: 0.666 AC: 3446 AN: 5176

South Asian (SAS) AF: 0.780 AC: 3760 AN: 4818

European-Finnish (FIN) AF: 0.783 AC: 8290 AN: 10584

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54850 AN: 67992

Other (OTH) AF: 0.849 AC: 1793 AN: 2112

Alfa AF: 0.826 Hom.: 8646

Bravo AF: 0.844

Asia WGS AF: 0.742 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.28
PhyloP100		-0.38
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: rs25855; hg19: chr5-156624400;