chr9-676569-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015158.5(KANK1):​c.-83-321C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 152,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Consequence

KANK1
NM_015158.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KANK1NM_015158.5 linkc.-83-321C>G 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>G intron_variant Intron 1 of 11 1 NM_015158.5 ENSP00000371734.2 Q14678-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152012
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000435
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152012
Hom.:
0
Cov.:
33
AF XY:
0.0000943
AC XY:
7
AN XY:
74230
show subpopulations
African (AFR)
AF:
0.000435
AC:
18
AN:
41352
American (AMR)
AF:
0.00
AC:
0
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10580
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68008
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
1704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.67
DANN
Benign
0.51
PhyloP100
-0.51
PromoterAI
-0.0050
Neutral

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