Variant chr9-676820-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.-83-70A>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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0880

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:

(HGNC:):

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=-0.84).

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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	c.-83-70A>G		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7 linkuse as main transcript	c.-83-70A>G		intron_variant		1	NM_015158.5	P2	Q14678-1
	ENST00000421645.2 linkuse as main transcript	n.219-2441T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81965

AN:

151970

Hom.:

25240

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.541

AC XY:

40183

AN XY:

74338

show subpopulations

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

LINK: link

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

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