4-48176797-C-T

Variant names:

• chr4-48176797-C-T
• rs11945978
• NM_003215.3:c.139-611G>A

Variant summary

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

The NM_003215.3(TEC):​c.139-611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,920 control chromosomes in the GnomAD database, including 11,955 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 0.38 (11955 hom., cov: 32)
• Consequence: TEC NM_003215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEC	NM_003215.3	c.139-611G>A		intron_variant	Intron 2 of 17	ENST00000381501.8	NP_003206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEC	ENST00000381501.8	c.139-611G>A		intron_variant	Intron 2 of 17	1	NM_003215.3	ENSP00000370912.3
TEC	ENST00000505452.5	n.139-611G>A		intron_variant	Intron 1 of 15	5		ENSP00000424567.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57590 AN: 151802 Hom.: 11942 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.379 AC: 57640 AN: 151920 Hom.: 11955 Cov.: 32 AF XY: 0.386 AC XY: 28681 AN XY: 74242

African (AFR) AF: 0.329 AC: 13636 AN: 41410

American (AMR) AF: 0.440 AC: 6708 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4669 AN: 5188

South Asian (SAS) AF: 0.525 AC: 2533 AN: 4822

European-Finnish (FIN) AF: 0.378 AC: 3982 AN: 10530

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23821 AN: 67940

Other (OTH) AF: 0.396 AC: 835 AN: 2106

Alfa AF: 0.370 Hom.: 1856

Bravo AF: 0.382

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.62
PhyloP100		0.47
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: rs11945978; hg19: chr4-48178814;