chr9-741307-G-A

Variant names:

• chr9-741307-G-A
• rs13286166
• NM_015158.5:c.3696+373G>A

Variant summary

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

The NM_015158.5(KANK1):​c.3696+373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,260 control chromosomes in the GnomAD database, including 6,399 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 0.27 (6399 hom., cov: 29)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 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.3696+373G>A		intron	N/A	NP_055973.2
	KANK1	NM_001256876.3		c.3696+373G>A		intron	N/A	NP_001243805.1
	KANK1	NM_001256877.3		c.3696+373G>A		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.3696+373G>A		intron	N/A	ENSP00000371734.2
	KANK1	ENST00000382303.5	TSL:1	c.3696+373G>A		intron	N/A	ENSP00000371740.1
	KANK1	ENST00000382293.7	TSL:1	c.3222+373G>A		intron	N/A	ENSP00000371730.3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41076 AN: 151142 Hom.: 6405 Cov.: 29

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.271 AC: 41054 AN: 151260 Hom.: 6399 Cov.: 29 AF XY: 0.268 AC XY: 19747 AN XY: 73780

African (AFR) AF: 0.138 AC: 5684 AN: 41300

American (AMR) AF: 0.198 AC: 3005 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3464

East Asian (EAS) AF: 0.154 AC: 794 AN: 5146

South Asian (SAS) AF: 0.342 AC: 1630 AN: 4764

European-Finnish (FIN) AF: 0.321 AC: 3288 AN: 10248

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24905 AN: 67824

Other (OTH) AF: 0.251 AC: 528 AN: 2100

Alfa AF: 0.347 Hom.: 4735

Bravo AF: 0.254

Asia WGS AF: 0.197 AC: 684 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		0.064
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: rs13286166; hg19: chr9-741307;