4-48224250-A-C

Position:

• chr4-48224250-A-C

Variant summary

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

The NM_003215.3(TEC):​c.138+4227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,768 control chromosomes in the GnomAD database, including 16,876 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 0.47 (16876 hom., cov: 32)
• Consequence: TEC NM_003215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

Genes affected

TEC (HGNC:11719): (tec protein tyrosine kinase) The protein encoded by this gene belongs to the Tec family of non-receptor protein-tyrosine kinases containing a pleckstrin homology domain. Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Tec kinase is an integral component of T cell signaling and has a distinct role in T cell activation. This gene may be associated with myelodysplastic syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEC	NM_003215.3	c.138+4227T>G		intron_variant		ENST00000381501.8	NP_003206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEC	ENST00000381501.8	c.138+4227T>G		intron_variant		1	NM_003215.3	ENSP00000370912	P1
TEC	ENST00000505452.5	c.138+4227T>G		intron_variant, NMD_transcript_variant		5		ENSP00000424567

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71016 AN: 151652 Hom.: 16854 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.468 AC: 71082 AN: 151768 Hom.: 16876 Cov.: 32 AF XY: 0.466 AC XY: 34541 AN XY: 74170

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.484

Alfa AF: 0.497 Hom.: 31367

Bravo AF: 0.480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.38

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: rs4694890; hg19: chr4-48226267;