16-87710885-T-C

Variant names:

• chr16-87710885-T-C
• rs3794668
• NM_017566.4:c.1044+350A>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.1044+350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 226,540 control chromosomes in the GnomAD database, including 54,416 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 0.70 (38133 hom., cov: 32)
  • Exomes 𝑓: 0.65 (16283 hom.)
• Consequence: KLHDC4 NM_017566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC4	NM_017566.4	MANE Select	c.1044+350A>G		intron	N/A	NP_060036.2
	KLHDC4	NM_001184856.2		c.951+350A>G		intron	N/A	NP_001171785.1
	KLHDC4	NM_001184854.2		c.873+350A>G		intron	N/A	NP_001171783.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC4	ENST00000270583.10	TSL:1 MANE Select	c.1044+350A>G		intron	N/A	ENSP00000270583.4
	KLHDC4	ENST00000347925.9	TSL:1	c.951+350A>G		intron	N/A	ENSP00000325717.5
	KLHDC4	ENST00000353170.9	TSL:1	c.873+350A>G		intron	N/A	ENSP00000262530.5

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107034 AN: 151954 Hom.: 38094 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.651 AC: 48478 AN: 74468 Hom.: 16283 Cov.: 0 AF XY: 0.648 AC XY: 24929 AN XY: 38462

African (AFR) AF: 0.792 AC: 2673 AN: 3376

American (AMR) AF: 0.574 AC: 2911 AN: 5068

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 1382 AN: 2068

East Asian (EAS) AF: 0.422 AC: 2263 AN: 5358

South Asian (SAS) AF: 0.591 AC: 4142 AN: 7006

European-Finnish (FIN) AF: 0.623 AC: 1605 AN: 2576

Middle Eastern (MID) AF: 0.612 AC: 197 AN: 322

European-Non Finnish (NFE) AF: 0.686 AC: 30593 AN: 44570

Other (OTH) AF: 0.658 AC: 2712 AN: 4124

GnomAD4 genome AF: 0.704 AC: 107130 AN: 152072 Hom.: 38133 Cov.: 32 AF XY: 0.697 AC XY: 51817 AN XY: 74312

African (AFR) AF: 0.798 AC: 33131 AN: 41502

American (AMR) AF: 0.620 AC: 9464 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3464

East Asian (EAS) AF: 0.485 AC: 2505 AN: 5162

South Asian (SAS) AF: 0.608 AC: 2934 AN: 4822

European-Finnish (FIN) AF: 0.634 AC: 6702 AN: 10566

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47676 AN: 67964

Other (OTH) AF: 0.674 AC: 1423 AN: 2110

Alfa AF: 0.693 Hom.: 13303

Bravo AF: 0.700

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.36
PhyloP100		-1.2
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: rs3794668; hg19: chr16-87744491;