rs3751726

Variant names:

• chr16-87698871-T-C
• rs3751726
• ENST00000567298.5:n.*2205A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000567298.5(KLHDC4):​n.*2205A>G variant causes a non coding transcript exon 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 ENST00000567298.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 5 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=-0.89).
• 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 rank	MANE	Protein	UniProt
KLHDC4	XR_001751943.2	n.6004A>G		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC4	ENST00000567298.5	n.*2205A>G		non_coding_transcript_exon_variant	Exon 17 of 17	5		ENSP00000457570.1
KLHDC4	ENST00000567298.5	n.*2205A>G		3_prime_UTR_variant	Exon 17 of 17	5		ENSP00000457570.1
KLHDC4	ENST00000446344.3	c.*2768A>G		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000392909.1
KLHDC4	ENST00000568444.1	n.216+329A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0606 AC: 4 AN: 66

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.0608 AC: 2526 AN: 41566

American (AMR) AF: 0.0640 AC: 980 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.160 AC: 830 AN: 5186

South Asian (SAS) AF: 0.171 AC: 826 AN: 4824

European-Finnish (FIN) AF: 0.0565 AC: 600 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0518 AC: 3526 AN: 68014

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0648 Hom.: 168

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
PhyloP100		-0.11
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

Other links and lift over

dbSNP: rs3751726; hg19: chr16-87732477;