rs12606529

Positions:

• chr18-32760397-T-C

Variant summary

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

The NM_020805.3(KLHL14):​c.947+9248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,438 control chromosomes in the GnomAD database, including 6,041 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 (6041 hom., cov: 32)
• Consequence: KLHL14 NM_020805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

Genes affected

KLHL14 (HGNC:29266): (kelch like family member 14) The protein encoded by this gene is a member of the Kelch-like gene family, whose members contain a BTB/POZ domain, a BACK domain, and several Kelch domains. The encoded protein possesses six Kelch domains and localizes to the endoplasmic reticulum, where it interacts with torsin-1A. [provided by RefSeq, Sep 2015]

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 (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL14	NM_020805.3	c.947+9248A>G		intron_variant		ENST00000359358.9	NP_065856.1
KLHL14	XM_047437684.1	c.947+9248A>G		intron_variant			XP_047293640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL14	ENST00000359358.9	c.947+9248A>G		intron_variant		1	NM_020805.3	ENSP00000352314.4
KLHL14	ENST00000358095.4	c.947+9248A>G		intron_variant		1		ENSP00000350808.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41270 AN: 151320 Hom.: 6038 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.273 AC: 41293 AN: 151438 Hom.: 6041 Cov.: 32 AF XY: 0.276 AC XY: 20443 AN XY: 73990

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.270

Alfa AF: 0.287 Hom.: 9773

Bravo AF: 0.273

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.61

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: rs12606529; hg19: chr18-30340360; COSMIC: COSV63833052;