NM_015158.5:c.-84+61163T>C

Variant names:

• chr9-565917-T-C
• rs7027930
• NM_015158.5:c.-84+61163T>C

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+61163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,110 control chromosomes in the GnomAD database, including 10,042 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 0.35 (10042 hom., cov: 32)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015158.5. 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
	KANK1	NM_015158.5	MANE Select	c.-84+61163T>C		intron	N/A	NP_055973.2
	KANK1	NM_001256876.3		c.-84+25250T>C		intron	N/A	NP_001243805.1
	KANK1	NM_001256877.3		c.-84+16196T>C		intron	N/A	NP_001243806.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.-84+61163T>C		intron	N/A	ENSP00000371734.2
	KANK1	ENST00000382303.5	TSL:1	c.-84+25250T>C		intron	N/A	ENSP00000371740.1
	KANK1	ENST00000619269.5	TSL:5	c.-84+61163T>C		intron	N/A	ENSP00000477725.2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53435 AN: 151992 Hom.: 10021 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.352 AC: 53495 AN: 152110 Hom.: 10042 Cov.: 32 AF XY: 0.352 AC XY: 26152 AN XY: 74358

African (AFR) AF: 0.462 AC: 19167 AN: 41470

American (AMR) AF: 0.455 AC: 6952 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1665 AN: 5178

South Asian (SAS) AF: 0.198 AC: 957 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3368 AN: 10596

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19553 AN: 67974

Other (OTH) AF: 0.336 AC: 711 AN: 2116

Alfa AF: 0.0598 Hom.: 1468

Bravo AF: 0.369

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		0.21
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: rs7027930; hg19: chr9-565917;