9-676745-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.-83-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 448,500 control chromosomes in the GnomAD database, including 840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (453 hom., cov: 33)
  • Exomes 𝑓: 0.022 (387 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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=-0.87).
• BP6: Variant 9-676745-A-G is Benign according to our data. Variant chr9-676745-A-G is described in ClinVar as [Benign]. Clinvar id is 1261637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK1	NM_015158.5	c.-83-145A>G		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-145A>G		intron_variant		1	NM_015158.5	P2
	ENST00000421645.2	n.219-2366T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7124 AN: 152134 Hom.: 454 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0219 AC: 6485 AN: 296248 Hom.: 387 AF XY: 0.0216 AC XY: 3369 AN XY: 156102

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0372

Gnomad4 ASJ exome AF: 0.00994

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0264

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.0308

GnomAD4 genome AF: 0.0468 AC: 7122 AN: 152252 Hom.: 453 Cov.: 33 AF XY: 0.0478 AC XY: 3559 AN XY: 74456

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0272 Hom.: 28

Bravo AF: 0.0527

Asia WGS AF: 0.127 AC: 443 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

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.036
Dann	Benign	0.42

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: rs12685605; hg19: chr9-676745;