rs141234076

Variant names:

• chr9-712526-A-G
• rs141234076
• NM_015158.5:c.1760A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-712526-A-G
• chr9-712526-A-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015158.5(KANK1):​c.1760A>G​(p.Glu587Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000704 in 1,614,146 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (4 hom.)
• Consequence: KANK1 NM_015158.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.68
• Publications: 2 publications found

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]

KANK1 Gene-Disease associations (from GenCC):

• spastic quadriplegic cerebral palsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy, spastic quadriplegic, 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004117012).
• BP6: Variant 9-712526-A-G is Benign according to our data. Variant chr9-712526-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 Unknown,AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	NM_015158.5	MANE Select	c.1760A>G	p.Glu587Gly	missense	Exon 3 of 12	NP_055973.2	Q14678-1
	KANK1	NM_001256876.3		c.1760A>G	p.Glu587Gly	missense	Exon 7 of 16	NP_001243805.1	Q14678-1
	KANK1	NM_001256877.3		c.1760A>G	p.Glu587Gly	missense	Exon 4 of 13	NP_001243806.1	Q14678-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.1760A>G	p.Glu587Gly	missense	Exon 3 of 12	ENSP00000371734.2	Q14678-1
	KANK1	ENST00000382303.5	TSL:1	c.1760A>G	p.Glu587Gly	missense	Exon 7 of 16	ENSP00000371740.1	Q14678-1
	KANK1	ENST00000382293.7	TSL:1	c.1286A>G	p.Glu429Gly	missense	Exon 2 of 11	ENSP00000371730.3	Q14678-2

Frequencies

GnomAD3 genomes AF: 0.000710 AC: 108 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00210 AC: 528 AN: 251342 AF XY: 0.00174

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000703 AC: 1027 AN: 1461886 Hom.: 4 Cov.: 64 AF XY: 0.000755 AC XY: 549 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00948 AC: 424 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 77 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00314 AC: 271 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1112010

Other (OTH) AF: 0.000530 AC: 32 AN: 60396

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74430

African (AFR) AF: 0.0000962 AC: 4 AN: 41560

American (AMR) AF: 0.00359 AC: 55 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4800

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000596 Hom.: 1

Bravo AF: 0.00118

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00189 AC: 229

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.7
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.15
Sift	Benign	0.031	D
Sift4G	Benign	0.12	T
Polyphen		0.0030	B
Vest4		0.26
MVP		0.29
ClinPred		0.043	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.40
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs141234076; hg19: chr9-712526;