chr9-745413-A-G

Variant names:

• chr9-745413-A-G
• rs3739586
• NM_015158.5:c.*178A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015158.5(KANK1):​c.*178A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 637,140 control chromosomes in the GnomAD database, including 146,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39609 hom., cov: 30)
  • Exomes 𝑓: 0.66 (106954 hom.)
• Consequence: KANK1 NM_015158.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69
• Publications: 11 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-745413-A-G is Benign according to our data. Variant chr9-745413-A-G is described in CliVar as Benign. Clinvar id is 1278047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.*178A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.*178A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108435 AN: 151854 Hom.: 39563 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.659 AC: 319918 AN: 485168 Hom.: 106954 Cov.: 7 AF XY: 0.658 AC XY: 167877 AN XY: 255102

African (AFR) AF: 0.875 AC: 11049 AN: 12626

American (AMR) AF: 0.655 AC: 13145 AN: 20076

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 7960 AN: 13256

East Asian (EAS) AF: 0.514 AC: 14198 AN: 27636

South Asian (SAS) AF: 0.649 AC: 30267 AN: 46628

European-Finnish (FIN) AF: 0.639 AC: 20535 AN: 32150

Middle Eastern (MID) AF: 0.680 AC: 1436 AN: 2112

European-Non Finnish (NFE) AF: 0.669 AC: 203953 AN: 304876

Other (OTH) AF: 0.673 AC: 17375 AN: 25808

GnomAD4 genome AF: 0.714 AC: 108530 AN: 151972 Hom.: 39609 Cov.: 30 AF XY: 0.708 AC XY: 52589 AN XY: 74270

African (AFR) AF: 0.877 AC: 36346 AN: 41466

American (AMR) AF: 0.624 AC: 9525 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3472

East Asian (EAS) AF: 0.581 AC: 2982 AN: 5136

South Asian (SAS) AF: 0.636 AC: 3063 AN: 4816

European-Finnish (FIN) AF: 0.621 AC: 6553 AN: 10554

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45589 AN: 67956

Other (OTH) AF: 0.689 AC: 1454 AN: 2110

Alfa AF: 0.683 Hom.: 45293

Bravo AF: 0.723

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

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	-0.88
CADD	Benign	0.098
DANN	Benign	0.31
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3739586; hg19: chr9-745413; COSMIC: COSV66529078;