9-676569-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015158.5(KANK1):​c.-83-321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,056 control chromosomes in the GnomAD database, including 19,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 19729 hom., cov: 33)

Consequence

KANK1
NM_015158.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.507

Publications

2 publications found
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 Gene-Disease associations (from GenCC):
  • spastic quadriplegic cerebral palsy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • cerebral palsy, spastic quadriplegic, 2
    Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 9-676569-C-T is Benign according to our data. Variant chr9-676569-C-T is described in ClinVar as [Benign]. Clinvar id is 1257104.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KANK1NM_015158.5 linkc.-83-321C>T intron_variant Intron 1 of 11 ENST00000382297.7 NP_055973.2 Q14678-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KANK1ENST00000382297.7 linkc.-83-321C>T intron_variant Intron 1 of 11 1 NM_015158.5 ENSP00000371734.2 Q14678-1

Frequencies

GnomAD3 genomes
AF:
0.490
AC:
74521
AN:
151938
Hom.:
19689
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.676
Gnomad AMI
AF:
0.446
Gnomad AMR
AF:
0.546
Gnomad ASJ
AF:
0.402
Gnomad EAS
AF:
0.582
Gnomad SAS
AF:
0.334
Gnomad FIN
AF:
0.471
Gnomad MID
AF:
0.462
Gnomad NFE
AF:
0.379
Gnomad OTH
AF:
0.451
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.491
AC:
74608
AN:
152056
Hom.:
19729
Cov.:
33
AF XY:
0.493
AC XY:
36611
AN XY:
74324
show subpopulations
African (AFR)
AF:
0.676
AC:
28005
AN:
41454
American (AMR)
AF:
0.547
AC:
8354
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.402
AC:
1396
AN:
3470
East Asian (EAS)
AF:
0.581
AC:
3009
AN:
5176
South Asian (SAS)
AF:
0.335
AC:
1615
AN:
4822
European-Finnish (FIN)
AF:
0.471
AC:
4982
AN:
10570
Middle Eastern (MID)
AF:
0.466
AC:
136
AN:
292
European-Non Finnish (NFE)
AF:
0.379
AC:
25741
AN:
67972
Other (OTH)
AF:
0.456
AC:
964
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1814
3627
5441
7254
9068
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
640
1280
1920
2560
3200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.344
Hom.:
1704
Bravo
AF:
0.507
Asia WGS
AF:
0.520
AC:
1807
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 29, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.6
DANN
Benign
0.62
PhyloP100
-0.51
PromoterAI
-0.0092
Neutral
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1570475; hg19: chr9-676569; API