rs7219773

Variant names:

• chr17-7379825-C-A
• rs7219773
• XM_011524045.3:c.-1014C>A

Variant summary

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

The XM_011524045.3(TNK1):​c.-1014C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,954 control chromosomes in the GnomAD database, including 13,258 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 (13258 hom., cov: 31)
• Consequence: TNK1 XM_011524045.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 20 publications found

Genes affected

TNK1 (HGNC:11940): (tyrosine kinase non receptor 1) The protein encoded by this gene belongs to the tyrosine protein kinase family. Tyrosine protein kinases are important regulators of intracellular signal transduction pathways, mediating cellular proliferation, survival, and development. This gene is highly expressed in fetal tissues and at lower levels in few adult tissues, thus may function in signaling pathways utilized broadly during fetal development, and more selectively in adult tissues. It plays a negative regulatory role in the Ras-Raf1-MAPK pathway, and knockout mice have been shown to develop spontaneous tumors, suggesting a role as a tumor suppressor gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK1	XM_011524045.3	c.-1014C>A		upstream_gene_variant			XP_011522347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62533 AN: 151834 Hom.: 13250 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.412 AC: 62565 AN: 151954 Hom.: 13258 Cov.: 31 AF XY: 0.407 AC XY: 30193 AN XY: 74268

African (AFR) AF: 0.366 AC: 15179 AN: 41442

American (AMR) AF: 0.342 AC: 5218 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5166

South Asian (SAS) AF: 0.579 AC: 2785 AN: 4810

European-Finnish (FIN) AF: 0.382 AC: 4030 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31401 AN: 67940

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.441 Hom.: 64966

Bravo AF: 0.397

Asia WGS AF: 0.440 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7219773; hg19: chr17-7283144;