9-676569-C-T

Position:

• chr9-676569-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-83-321C>T		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-321C>T		intron_variant		1	NM_015158.5	ENSP00000371734	P2
	ENST00000421645.2	n.219-2190G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.456

Alfa AF: 0.332 Hom.: 1515

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.62

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: rs1570475; hg19: chr9-676569;