9-676820-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015158.5(KANK1):c.-83-70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 622,100 control chromosomes in the GnomAD database, including 68,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (25296 hom., cov: 32)
  • Exomes 𝑓: 0.41 (43039 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-676820-A-G is Benign according to our data. Variant chr9-676820-A-G is described in ClinVar as [Benign]. Clinvar id is 1261697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK1	NM_015158.5	c.-83-70A>G		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-70A>G		intron_variant		1	NM_015158.5	P2
	ENST00000421645.2	n.219-2441T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81965 AN: 151970 Hom.: 25240 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.413 AC: 194330 AN: 470012 Hom.: 43039 AF XY: 0.406 AC XY: 101888 AN XY: 251092

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.564

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.540 AC: 82081 AN: 152088 Hom.: 25296 Cov.: 32 AF XY: 0.541 AC XY: 40183 AN XY: 74338

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.491

Alfa AF: 0.412 Hom.: 6642

Bravo AF: 0.562

Asia WGS AF: 0.535 AC: 1859 AN: 3478

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

Nov 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.9
Dann	Benign	0.67

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: rs1570474; hg19: chr9-676820; COSMIC: COSV63210967;