rs8729

Positions:

• chr9-21331120-C-T

Variant summary

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

The NM_018847.4(KLHL9):​c.*1886G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,352 control chromosomes in the GnomAD database, including 5,608 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 0.26 (5601 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7 hom.)
• Consequence: KLHL9 NM_018847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

Genes affected

KLHL9 (HGNC:18732): (kelch like family member 9) This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes. [provided by RefSeq, Jul 2016]

LOC107987053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL9	NM_018847.4	c.*1886G>A		3_prime_UTR_variant	1/1	ENST00000359039.5	NP_061335.1
LOC107987053	XR_001746634.2	n.472-5501C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL9	ENST00000359039	c.*1886G>A		3_prime_UTR_variant	1/1		NM_018847.4	ENSP00000351933.4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39844 AN: 151804 Hom.: 5592 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.179 AC: 77 AN: 430 Hom.: 7 Cov.: 0 AF XY: 0.171 AC XY: 44 AN XY: 258

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.263 AC: 39894 AN: 151922 Hom.: 5601 Cov.: 32 AF XY: 0.262 AC XY: 19438 AN XY: 74258

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.256

Alfa AF: 0.255 Hom.: 1748

Bravo AF: 0.278

Asia WGS AF: 0.299 AC: 1036 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.70

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: rs8729; hg19: chr9-21331119;