9-649750-C-T

Position:

• chr9-649750-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382297.7(KANK1):​c.-83-27140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,982 control chromosomes in the GnomAD database, including 33,422 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 0.63 (33422 hom., cov: 31)
• Consequence: KANK1 ENST00000382297.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-83-27140C>T		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-27140C>T		intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96302 AN: 151864 Hom.: 33365 Cov.: 31

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.634 AC: 96423 AN: 151982 Hom.: 33422 Cov.: 31 AF XY: 0.635 AC XY: 47178 AN XY: 74272

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.605

Alfa AF: 0.489 Hom.: 9001

Bravo AF: 0.663

Asia WGS AF: 0.701 AC: 2435 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	6.8
DANN	Benign	0.56

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: rs2031175; hg19: chr9-649750; COSMIC: COSV63215017;