rs12606529

Variant names:

• chr18-32760397-T-C
• rs12606529
• NM_020805.3:c.947+9248A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLHL14	NM_020805.3	c.947+9248A>G		intron_variant	Intron 2 of 8	ENST00000359358.9	NP_065856.1
KLHL14	XM_047437684.1	c.947+9248A>G		intron_variant	Intron 2 of 3		XP_047293640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL14	ENST00000359358.9	c.947+9248A>G		intron_variant	Intron 2 of 8	1	NM_020805.3	ENSP00000352314.4
KLHL14	ENST00000358095.4	c.947+9248A>G		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.186 AC: 7631 AN: 41106

American (AMR) AF: 0.360 AC: 5485 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 904 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1984 AN: 5144

South Asian (SAS) AF: 0.426 AC: 2041 AN: 4788

European-Finnish (FIN) AF: 0.298 AC: 3123 AN: 10496

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19305 AN: 67866

Other (OTH) AF: 0.270 AC: 569 AN: 2108

Alfa AF: 0.283 Hom.: 22264

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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