rs7019412

Positions:

• chr9-498343-G-A
• chr9-498343-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000382303.5(KANK1):​c.-362+25070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 152,236 control chromosomes in the GnomAD database, including 17 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 0.0076 (17 hom., cov: 32)
• Consequence: KANK1 ENST00000382303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

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=-0.97).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00763 (1161/152236) while in subpopulation AFR AF= 0.0253 (1050/41520). AF 95% confidence interval is 0.024. There are 17 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_001256876.3	c.-362+25070G>A		intron_variant			NP_001243805.1
KANK1	XM_047423040.1	c.-84+25070G>A		intron_variant			XP_047278996.1
KANK1	XM_047423041.1	c.-566+25070G>A		intron_variant			XP_047278997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382303.5	c.-362+25070G>A		intron_variant		1		ENSP00000371740	P2
KANK1	ENST00000688973.1	n.405+25070G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1157 AN: 152118 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00334

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

GnomAD4 genome AF: 0.00763 AC: 1161 AN: 152236 Hom.: 17 Cov.: 32 AF XY: 0.00752 AC XY: 560 AN XY: 74428

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.00859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.063
DANN	Benign	0.73

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: rs7019412; hg19: chr9-498343;