16-87698871-T-C

Position:

• chr16-87698871-T-C

Variant summary

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

The ENST00000446344.3(KLHDC4):​c.*2768A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,382 control chromosomes in the GnomAD database, including 390 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 0.064 (389 hom., cov: 33)
  • Exomes 𝑓: 0.083 (1 hom.)
• Consequence: KLHDC4 ENST00000446344.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHDC4	XR_001751943.2	n.6004A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHDC4	ENST00000446344.3	c.*2768A>G		3_prime_UTR_variant	1/1
KLHDC4	ENST00000567298.5	c.*2205A>G		3_prime_UTR_variant, NMD_transcript_variant	17/17	5
KLHDC4	ENST00000568444.1	n.216+329A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9737 AN: 152180 Hom.: 388 Cov.: 33

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0685

GnomAD4 exome AF: 0.0833 AC: 7 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.0968 AC XY: 6 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0606

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0640 AC: 9742 AN: 152298 Hom.: 389 Cov.: 33 AF XY: 0.0680 AC XY: 5061 AN XY: 74460

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.0640

Gnomad4 ASJ AF: 0.0760

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0518

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0595 Hom.: 83

Bravo AF: 0.0643

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3751726; hg19: chr16-87732477;