9-676741-A-G

Position:

• chr9-676741-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.-83-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 443,038 control chromosomes in the GnomAD database, including 1,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (461 hom., cov: 32)
  • Exomes 𝑓: 0.079 (1075 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-676741-A-G is Benign according to our data. Variant chr9-676741-A-G is described in ClinVar as [Benign]. Clinvar id is 1279682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-83-149A>G		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-149A>G		intron_variant		1	NM_015158.5	ENSP00000371734	P2
	ENST00000421645.2	n.219-2362T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10616 AN: 152106 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0792 AC: 23027 AN: 290814 Hom.: 1075 AF XY: 0.0781 AC XY: 11967 AN XY: 153280

Gnomad4 AFR exome AF: 0.0321

Gnomad4 AMR exome AF: 0.0450

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.0473

Gnomad4 SAS exome AF: 0.0539

Gnomad4 FIN exome AF: 0.0865

Gnomad4 NFE exome AF: 0.0903

Gnomad4 OTH exome AF: 0.0752

GnomAD4 genome AF: 0.0698 AC: 10628 AN: 152224 Hom.: 461 Cov.: 32 AF XY: 0.0693 AC XY: 5156 AN XY: 74434

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0581

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0403 Hom.: 56

Bravo AF: 0.0638

Asia WGS AF: 0.0440 AC: 151 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.24

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: rs10975740; hg19: chr9-676741;