9-676569-C-T

Variant names:

• chr9-676569-C-T
• rs1570475
• NM_015158.5:c.-83-321C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507
• Publications: 2 publications found

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

ENSG00000227914 (HGNC:58139):

ACMG classification

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
KANK1	NM_015158.5	c.-83-321C>T		intron_variant	Intron 1 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-321C>T		intron_variant	Intron 1 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74521 AN: 151938 Hom.: 19689 Cov.: 33

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

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

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

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

Other links and lift over

dbSNP: rs1570475; hg19: chr9-676569;