rs4843689

Positions:

• chr16-87731551-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017566.4(KLHDC4):​c.507-907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,772 control chromosomes in the GnomAD database, including 1,671 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 0.12 (1671 hom., cov: 30)
• Consequence: KLHDC4 NM_017566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

KLHDC4 (HGNC:25272): (kelch domain containing 4)

KLHDC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC4	NM_017566.4	c.507-907A>G		intron_variant		ENST00000270583.10	NP_060036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC4	ENST00000270583.10	c.507-907A>G		intron_variant		1	NM_017566.4	ENSP00000270583.4
KLHDC4	ENST00000567298.5	n.507-907A>G		intron_variant		5		ENSP00000457570.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18111 AN: 151654 Hom.: 1662 Cov.: 30

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.120 AC: 18144 AN: 151772 Hom.: 1671 Cov.: 30 AF XY: 0.120 AC XY: 8884 AN XY: 74168

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0860 Hom.: 232

Bravo AF: 0.132

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs4843689; hg19: chr16-87765157;