rs3739586

Positions:

• chr9-745413-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.*178A>G		3_prime_UTR_variant	12/12	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.*178A>G		3_prime_UTR_variant	12/12	1	NM_015158.5	ENSP00000371734	P2

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

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.655

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.649

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.673

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

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.689

Alfa AF: 0.675 Hom.: 33675

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.098
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs3739586; hg19: chr9-745413; COSMIC: COSV66529078;