rs4733065

Variant names:

• chr8-27450487-G-A
• rs4733065
• NM_173176.3:c.2341-262G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-27450487-G-A
• chr8-27450487-G-C

Variant summary

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

The NM_173176.3(PTK2B):​c.2341-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,124 control chromosomes in the GnomAD database, including 13,335 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 0.41 (13335 hom., cov: 33)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 8 publications found

Genes affected

PTK2B (HGNC:9612): (protein tyrosine kinase 2 beta) This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.2341-262G>A		intron_variant	Intron 24 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.2341-262G>A		intron_variant	Intron 24 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62157 AN: 152006 Hom.: 13325 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.409 AC: 62203 AN: 152124 Hom.: 13335 Cov.: 33 AF XY: 0.410 AC XY: 30518 AN XY: 74382

African (AFR) AF: 0.276 AC: 11447 AN: 41486

American (AMR) AF: 0.415 AC: 6342 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1820 AN: 5180

South Asian (SAS) AF: 0.398 AC: 1918 AN: 4822

European-Finnish (FIN) AF: 0.528 AC: 5582 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31544 AN: 67986

Other (OTH) AF: 0.460 AC: 972 AN: 2114

Alfa AF: 0.302 Hom.: 832

Bravo AF: 0.398

Asia WGS AF: 0.380 AC: 1321 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	0.026
DANN	Benign	0.66
PhyloP100		-0.94
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: rs4733065; hg19: chr8-27308004;