rs4843689

Variant names:

• chr16-87731551-T-C
• rs4843689
• NM_017566.4:c.507-907A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017566.4. 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
	KLHDC4	NM_017566.4	MANE Select	c.507-907A>G		intron	N/A	NP_060036.2
	KLHDC4	NM_001184856.2		c.507-4627A>G		intron	N/A	NP_001171785.1	Q8TBB5-3
	KLHDC4	NM_001184854.2		c.336-907A>G		intron	N/A	NP_001171783.1	Q8TBB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC4	ENST00000270583.10	TSL:1 MANE Select	c.507-907A>G		intron	N/A	ENSP00000270583.4	Q8TBB5-1
	KLHDC4	ENST00000347925.9	TSL:1	c.507-4627A>G		intron	N/A	ENSP00000325717.5	Q8TBB5-3
	KLHDC4	ENST00000353170.9	TSL:1	c.336-907A>G		intron	N/A	ENSP00000262530.5	Q8TBB5-2

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

African (AFR) AF: 0.253 AC: 10453 AN: 41334

American (AMR) AF: 0.100 AC: 1525 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3470

East Asian (EAS) AF: 0.156 AC: 807 AN: 5164

South Asian (SAS) AF: 0.155 AC: 743 AN: 4806

European-Finnish (FIN) AF: 0.0133 AC: 140 AN: 10538

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3804 AN: 67948

Other (OTH) AF: 0.119 AC: 251 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.35
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs4843689; hg19: chr16-87765157;