4-48258627-A-G

Variant summary

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

The NM_003215.3(TEC):c.-46+11125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,014 control chromosomes in the GnomAD database, including 23,151 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 0.55 (23151 hom., cov: 32)
• Consequence: TEC NM_003215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEC	NM_003215.3	c.-46+11125T>C		intron_variant		ENST00000381501.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEC	ENST00000381501.8	c.-46+11125T>C		intron_variant		1	NM_003215.3	P1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83373 AN: 151896 Hom.: 23119 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.549 AC: 83451 AN: 152014 Hom.: 23151 Cov.: 32 AF XY: 0.552 AC XY: 41039 AN XY: 74294

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.558

Alfa AF: 0.530 Hom.: 39066

Bravo AF: 0.553

Asia WGS AF: 0.644 AC: 2236 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	1.1
Dann	Benign	0.31

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: rs1472971; hg19: chr4-48260644;