NM_019117.5:c.728-145C>T

Variant names:

• chrX-87617787-C-T
• rs5924068
• NM_019117.5:c.728-145C>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.728-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 441,702 control chromosomes in the GnomAD database, including 25,621 homozygotes. There are 54,232 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 0.38 (5973 hom., 11872 hem., cov: 23)
  • Exomes 𝑓: 0.41 (19648 hom. 42360 hem.)
• Consequence: KLHL4 NM_019117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL4	NM_019117.5	MANE Select	c.728-145C>T		intron	N/A	NP_061990.2
	KLHL4	NM_057162.3		c.728-145C>T		intron	N/A	NP_476503.1	Q9C0H6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL4	ENST00000373119.9	TSL:1 MANE Select	c.728-145C>T		intron	N/A	ENSP00000362211.4	Q9C0H6-1
	KLHL4	ENST00000373114.4	TSL:1	c.728-145C>T		intron	N/A	ENSP00000362206.4	Q9C0H6-2
	KLHL4	ENST00000858463.1		c.728-145C>T		intron	N/A	ENSP00000528522.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 41444 AN: 110365 Hom.: 5980 Cov.: 23

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.482

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.408 AC: 135254 AN: 331292 Hom.: 19648 AF XY: 0.411 AC XY: 42360 AN XY: 103178

African (AFR) AF: 0.273 AC: 2675 AN: 9789

American (AMR) AF: 0.278 AC: 3820 AN: 13734

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 4681 AN: 9537

East Asian (EAS) AF: 0.252 AC: 5847 AN: 23237

South Asian (SAS) AF: 0.299 AC: 5931 AN: 19843

European-Finnish (FIN) AF: 0.363 AC: 10933 AN: 30135

Middle Eastern (MID) AF: 0.473 AC: 642 AN: 1357

European-Non Finnish (NFE) AF: 0.455 AC: 92894 AN: 204215

Other (OTH) AF: 0.403 AC: 7831 AN: 19445

GnomAD4 genome AF: 0.375 AC: 41435 AN: 110410 Hom.: 5973 Cov.: 23 AF XY: 0.363 AC XY: 11872 AN XY: 32716

African (AFR) AF: 0.267 AC: 8133 AN: 30405

American (AMR) AF: 0.331 AC: 3413 AN: 10311

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1275 AN: 2628

East Asian (EAS) AF: 0.226 AC: 787 AN: 3482

South Asian (SAS) AF: 0.290 AC: 768 AN: 2651

European-Finnish (FIN) AF: 0.353 AC: 2033 AN: 5765

Middle Eastern (MID) AF: 0.480 AC: 98 AN: 204

European-Non Finnish (NFE) AF: 0.454 AC: 23965 AN: 52802

Other (OTH) AF: 0.386 AC: 577 AN: 1494

Alfa AF: 0.407 Hom.: 2764

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.44
PhyloP100		-1.0
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: rs5924068; hg19: chrX-86872790;