4-48218822-G-A

Variant names:

• chr4-48218822-G-A
• rs2664035
• NM_003215.3:c.138+9655C>T

Variant summary

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

The NM_003215.3(TEC):​c.138+9655C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,932 control chromosomes in the GnomAD database, including 12,553 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 0.40 (12553 hom., cov: 31)
• Consequence: TEC NM_003215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 22 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003215.3. 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
	TEC	NM_003215.3	MANE Select	c.138+9655C>T		intron	N/A	NP_003206.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEC	ENST00000381501.8	TSL:1 MANE Select	c.138+9655C>T		intron	N/A	ENSP00000370912.3
	TEC	ENST00000505452.5	TSL:5	n.138+9655C>T		intron	N/A	ENSP00000424567.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61322 AN: 151812 Hom.: 12538 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.404 AC: 61388 AN: 151932 Hom.: 12553 Cov.: 31 AF XY: 0.400 AC XY: 29700 AN XY: 74242

African (AFR) AF: 0.436 AC: 18040 AN: 41422

American (AMR) AF: 0.443 AC: 6761 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1366 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1871 AN: 5150

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3627 AN: 10558

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27073 AN: 67942

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.408 Hom.: 23976

Bravo AF: 0.417

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		0.33
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: rs2664035; hg19: chr4-48220839;