X-87617650-C-T

Variant names:

• chrX-87617650-C-T
• rs5924066
• NM_019117.5:c.728-282C>T

Variant summary

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

The NM_019117.5(KLHL4):​c.728-282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 110,314 control chromosomes in the GnomAD database, including 5,969 homozygotes. There are 11,724 hemizygotes in GnomAD. 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 0.37 (5969 hom., 11724 hem., cov: 23)
• Consequence: KLHL4 NM_019117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 1 publications found

Genes affected

KLHL4 (HGNC:6355): (kelch like family member 4) This gene encodes a member of the kelch family of proteins, which are characterized by kelch repeat motifs and a POZ/BTB protein-binding domain. It is thought that kelch repeats are actin binding domains. However, the specific function of this protein has not been determined. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL4	NM_019117.5	c.728-282C>T		intron_variant	Intron 3 of 10	ENST00000373119.9	NP_061990.2
KLHL4	NM_057162.3	c.728-282C>T		intron_variant	Intron 3 of 10		NP_476503.1
KLHL4	XR_938403.3	n.820-282C>T		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL4	ENST00000373119.9	c.728-282C>T		intron_variant	Intron 3 of 10	1	NM_019117.5	ENSP00000362211.4
KLHL4	ENST00000373114.4	c.728-282C>T		intron_variant	Intron 3 of 10	1		ENSP00000362206.4
KLHL4	ENST00000652270.1	n.728-282C>T		intron_variant	Intron 3 of 11			ENSP00000498718.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 41280 AN: 110264 Hom.: 5976 Cov.: 23

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.374 AC: 41269 AN: 110314 Hom.: 5969 Cov.: 23 AF XY: 0.359 AC XY: 11724 AN XY: 32656

African (AFR) AF: 0.267 AC: 8132 AN: 30488

American (AMR) AF: 0.330 AC: 3407 AN: 10337

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1273 AN: 2619

East Asian (EAS) AF: 0.222 AC: 771 AN: 3473

South Asian (SAS) AF: 0.287 AC: 748 AN: 2610

European-Finnish (FIN) AF: 0.349 AC: 2012 AN: 5760

Middle Eastern (MID) AF: 0.476 AC: 100 AN: 210

European-Non Finnish (NFE) AF: 0.453 AC: 23864 AN: 52629

Other (OTH) AF: 0.380 AC: 578 AN: 1520

Alfa AF: 0.406 Hom.: 13798

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-0.024
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: rs5924066; hg19: chrX-86872653;