rs7027930

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-84+61163T>C		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+61163T>C		intron_variant	Intron 1 of 11	1	NM_015158.5	ENSP00000371734.2

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.336

Alfa AF: 0.0699 Hom.: 1468

Bravo AF: 0.369

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs7027930; hg19: chr9-565917;