chr9-740769-C-CTT

Position:

• chr9-740769-C-CTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015158.5(KANK1):​c.3554-6_3554-5dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (49 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2097/144728) while in subpopulation AFR AF= 0.0492 (1952/39700). AF 95% confidence interval is 0.0474. There are 49 homozygotes in gnomad4. There are 968 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2097 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-6_3554-5dup		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-6_3554-5dup		intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2094 AN: 144682 Hom.: 50 Cov.: 0

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.000870

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000167

Gnomad OTH AF: 0.0150

GnomAD4 exome AF: 0.00146 AC: 1979 AN: 1358260 Hom.: 0 Cov.: 0 AF XY: 0.00135 AC XY: 912 AN XY: 675220

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.00381

Gnomad4 ASJ exome AF: 0.00141

Gnomad4 EAS exome AF: 0.00296

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.00164

Gnomad4 NFE exome AF: 0.000485

Gnomad4 OTH exome AF: 0.00239

GnomAD4 genome AF: 0.0145 AC: 2097 AN: 144728 Hom.: 49 Cov.: 0 AF XY: 0.0138 AC XY: 968 AN XY: 70104

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.00659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00125

Gnomad4 SAS AF: 0.000872

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000167

Gnomad4 OTH AF: 0.0150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58169581; hg19: chr9-740769;