9-517715-C-T

Variant names:

• chr9-517715-C-T
• rs1928415
• NM_015158.5:c.-84+12961C>T

Variant summary

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

The NM_015158.5(KANK1):​c.-84+12961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 147,198 control chromosomes in the GnomAD database, including 10,541 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 0.29 (10541 hom., cov: 29)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 8 publications found

Genes affected

KANK1 (HGNC:19309): (KN motif and ankyrin repeat domains 1) The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

KANK1 Gene-Disease associations (from GenCC):

• spastic quadriplegic cerebral palsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy, spastic quadriplegic, 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-84+12961C>T		intron_variant	Intron 1 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-84+12961C>T		intron_variant	Intron 1 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 43065 AN: 147144 Hom.: 10518 Cov.: 29

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.00261

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.293 AC: 43132 AN: 147198 Hom.: 10541 Cov.: 29 AF XY: 0.288 AC XY: 20571 AN XY: 71412

African (AFR) AF: 0.669 AC: 26397 AN: 39452

American (AMR) AF: 0.144 AC: 2109 AN: 14640

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 301 AN: 3448

East Asian (EAS) AF: 0.00262 AC: 13 AN: 4956

South Asian (SAS) AF: 0.225 AC: 1047 AN: 4648

European-Finnish (FIN) AF: 0.150 AC: 1412 AN: 9400

Middle Eastern (MID) AF: 0.118 AC: 33 AN: 280

European-Non Finnish (NFE) AF: 0.163 AC: 11024 AN: 67458

Other (OTH) AF: 0.219 AC: 440 AN: 2010

Alfa AF: 0.185 Hom.: 7497

Bravo AF: 0.308

Asia WGS AF: 0.135 AC: 475 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.8
DANN	Benign	0.86
PhyloP100		0.31
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: rs1928415; hg19: chr9-517715;