Variant 9-676745-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.39

Variant links:

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]

KANK1 links:

ENSG00000227914 (HGNC:58139):

ENSG00000227914 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
KANK1	NM_015158.5 link	c.-83-145A>G		intron_variant		ENST00000382297.7	NP_055973.2	Q14678-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7 link	c.-83-145A>G		intron_variant		1	NM_015158.5	ENSP00000371734.2		Q14678-1

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7124

AN:

152134

Hom.:

454

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0478

AC XY:

3559

AN XY:

74456

show subpopulations

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.:

Bravo

AF:

0.0527

Asia WGS

AF:

0.127

AC:

443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 03, 2020	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over