9-677141-A-G

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.37+132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 801,630 control chromosomes in the GnomAD database, including 1,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (405 hom., cov: 33)
  • Exomes 𝑓: 0.017 (635 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.388

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=-0.67).
• BP6: Variant 9-677141-A-G is Benign according to our data. Variant chr9-677141-A-G is described in ClinVar as [Benign]. Clinvar id is 1259934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK1	NM_015158.5	c.37+132A>G		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7	c.37+132A>G		intron_variant		1	NM_015158.5	P2
	ENST00000421645.2	n.219-2762T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6778 AN: 152168 Hom.: 406 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0174 AC: 11280 AN: 649344 Hom.: 635 AF XY: 0.0173 AC XY: 5794 AN XY: 334532

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.00932

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0278

Gnomad4 FIN exome AF: 0.0318

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.0296

GnomAD4 genome AF: 0.0445 AC: 6776 AN: 152286 Hom.: 405 Cov.: 33 AF XY: 0.0456 AC XY: 3394 AN XY: 74468

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0333 Hom.: 30

Bravo AF: 0.0499

Asia WGS AF: 0.122 AC: 423 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

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.1
Dann	Benign	0.79

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: rs2296054; hg19: chr9-677141;