chr9-740769-CTTTTTTT-C

Position:

• chr9-740769-CTTTTTTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015158.5(KANK1):​c.3554-11_3554-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 1,461,882 control chromosomes in the GnomAD database, including 1,535 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (690 hom., cov: 0)
  • Exomes 𝑓: 0.063 (845 hom.)
• Consequence: KANK1 NM_015158.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.56

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 -10 ACMG points.

• BP6: Variant 9-740769-CTTTTTTT-C is Benign according to our data. Variant chr9-740769-CTTTTTTT-C is described in ClinVar as [Benign]. Clinvar id is 1269588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-11_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-11_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 11756 AN: 144642 Hom.: 691 Cov.: 0

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0421

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0405

Gnomad EAS AF: 0.00166

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0717

GnomAD4 exome AF: 0.0632 AC: 83259 AN: 1317194 Hom.: 845 AF XY: 0.0656 AC XY: 42929 AN XY: 654110

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0446

Gnomad4 ASJ exome AF: 0.0469

Gnomad4 EAS exome AF: 0.00268

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0682

Gnomad4 NFE exome AF: 0.0573

Gnomad4 OTH exome AF: 0.0684

GnomAD4 genome AF: 0.0814 AC: 11778 AN: 144688 Hom.: 690 Cov.: 0 AF XY: 0.0812 AC XY: 5689 AN XY: 70080

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0405

Gnomad4 EAS AF: 0.00166

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0479

Gnomad4 OTH AF: 0.0714

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2020

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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;