X-87617787-C-A

Variant names:

• chrX-87617787-C-A
• rs5924068
• NM_019117.5:c.728-145C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019117.5(KLHL4):​c.728-145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000301 in 331,677 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000030 (0 hom. 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL4	NM_019117.5	c.728-145C>A		intron_variant	Intron 3 of 10	ENST00000373119.9	NP_061990.2
KLHL4	NM_057162.3	c.728-145C>A		intron_variant	Intron 3 of 10		NP_476503.1
KLHL4	XR_938403.3	n.820-145C>A		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL4	ENST00000373119.9	c.728-145C>A		intron_variant	Intron 3 of 10	1	NM_019117.5	ENSP00000362211.4
KLHL4	ENST00000373114.4	c.728-145C>A		intron_variant	Intron 3 of 10	1		ENSP00000362206.4
KLHL4	ENST00000652270.1	n.728-145C>A		intron_variant	Intron 3 of 11			ENSP00000498718.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000301 AC: 1 AN: 331677 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 103215

African (AFR) AF: 0.00 AC: 0 AN: 9801

American (AMR) AF: 0.00 AC: 0 AN: 13738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9543

East Asian (EAS) AF: 0.00 AC: 0 AN: 23246

South Asian (SAS) AF: 0.00 AC: 0 AN: 19865

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30169

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1357

European-Non Finnish (NFE) AF: 0.00000489 AC: 1 AN: 204490

Other (OTH) AF: 0.00 AC: 0 AN: 19468

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.33
PhyloP100		-1.0

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;