rs9304112

Positions:

• chr18-32708025-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.1070-12473A>G 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 152,154 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: -1.11

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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/exons	MANE	UniProt
KLHL14	NM_020805.3	c.1070-12473A>G		intron_variant		ENST00000359358.9
LOC112268208	XR_002958196.2	n.207+19146T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL14	ENST00000359358.9	c.1070-12473A>G		intron_variant		1	NM_020805.3	P1
	ENST00000646805.1	n.817-29326T>C		intron_variant, non_coding_transcript_variant
	ENST00000654761.1	n.185-29326T>C		intron_variant, non_coding_transcript_variant
	ENST00000670534.1	n.210+19146T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20635 AN: 152038 Hom.: 4251 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.00800

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.136 AC: 20709 AN: 152154 Hom.: 4272 Cov.: 32 AF XY: 0.132 AC XY: 9852 AN XY: 74408

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00809

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.00800

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0320 Hom.: 796

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	-0.95
CADD	Benign	1.7
DANN	Benign	0.37

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: rs9304112; hg19: chr18-30287988;