5-157237968-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005546.4(ITK):​c.769-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 692,362 control chromosomes in the GnomAD database, including 27,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (5012 hom., cov: 32)
  • Exomes 𝑓: 0.28 (22060 hom.)
• Consequence: ITK NM_005546.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-157237968-C-T is Benign according to our data. Variant chr5-157237968-C-T is described in ClinVar as Benign. ClinVar VariationId is 1264492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35570 AN: 152010 Hom.: 5021 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.279 AC: 150514 AN: 540234 Hom.: 22060 AF XY: 0.276 AC XY: 80295 AN XY: 291420

African (AFR) AF: 0.0852 AC: 1296 AN: 15216

American (AMR) AF: 0.297 AC: 10058 AN: 33872

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 5698 AN: 19150

East Asian (EAS) AF: 0.213 AC: 6686 AN: 31378

South Asian (SAS) AF: 0.209 AC: 12850 AN: 61504

European-Finnish (FIN) AF: 0.260 AC: 10621 AN: 40924

Middle Eastern (MID) AF: 0.297 AC: 777 AN: 2614

European-Non Finnish (NFE) AF: 0.308 AC: 94235 AN: 306286

Other (OTH) AF: 0.283 AC: 8293 AN: 29290

GnomAD4 genome AF: 0.234 AC: 35571 AN: 152128 Hom.: 5012 Cov.: 32 AF XY: 0.231 AC XY: 17144 AN XY: 74370

African (AFR) AF: 0.0810 AC: 3366 AN: 41538

American (AMR) AF: 0.305 AC: 4654 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1048 AN: 5172

South Asian (SAS) AF: 0.192 AC: 926 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20912 AN: 67966

Other (OTH) AF: 0.272 AC: 575 AN: 2116

Alfa AF: 0.267 Hom.: 3030

Bravo AF: 0.233

Asia WGS AF: 0.202 AC: 706 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.057
DANN	Benign	0.71
PhyloP100		-0.61
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: rs30117; hg19: chr5-156664978; COSMIC: COSV68435343; COSMIC: COSV68435343;