chr9-741307-G-A

Position:

• chr9-741307-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015158.5(KANK1):​c.3696+373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,260 control chromosomes in the GnomAD database, including 6,399 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6399 hom., cov: 29)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK1	NM_015158.5	c.3696+373G>A		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7	c.3696+373G>A		intron_variant		1	NM_015158.5	P2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41076 AN: 151142 Hom.: 6405 Cov.: 29

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41054 AN: 151260 Hom.: 6399 Cov.: 29 AF XY: 0.268 AC XY: 19747 AN XY: 73780

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.251

Alfa AF: 0.347 Hom.: 4254

Bravo AF: 0.254

Asia WGS AF: 0.197 AC: 684 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.76

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: rs13286166; hg19: chr9-741307;