rs9304111

Variant names:

• chr18-32707969-A-G
• rs9304111
• NM_020805.3:c.1070-12417T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020805.3(KLHL14):​c.1070-12417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,170 control chromosomes in the GnomAD database, including 4,272 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 0.14 (4272 hom., cov: 32)
• Consequence: KLHL14 NM_020805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 0 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]

ENSG00000285095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL14	NM_020805.3	c.1070-12417T>C		intron_variant	Intron 3 of 8	ENST00000359358.9	NP_065856.1
LOC112268208	XR_002958196.2	n.207+19090A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL14	ENST00000359358.9	c.1070-12417T>C		intron_variant	Intron 3 of 8	1	NM_020805.3	ENSP00000352314.4
ENSG00000285095	ENST00000646805.1	n.817-29382A>G		intron_variant	Intron 4 of 6
ENSG00000285095	ENST00000654761.1	n.185-29382A>G		intron_variant	Intron 2 of 2
ENSG00000285095	ENST00000670534.1	n.210+19090A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20645 AN: 152052 Hom.: 4252 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0981

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

GnomAD4 genome AF: 0.136 AC: 20718 AN: 152170 Hom.: 4272 Cov.: 32 AF XY: 0.132 AC XY: 9854 AN XY: 74396

African (AFR) AF: 0.446 AC: 18491 AN: 41448

American (AMR) AF: 0.0528 AC: 807 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5178

South Asian (SAS) AF: 0.0484 AC: 234 AN: 4830

European-Finnish (FIN) AF: 0.00782 AC: 83 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 784 AN: 68022

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0715 Hom.: 2967

Bravo AF: 0.151

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		0.28
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: rs9304111; hg19: chr18-30287932;