rs16976587

Positions:

• chr16-27203663-G-A
• chr16-27203663-G-C

Variant summary

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

The ENST00000286096.9(KDM8):​c.-32+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 164,834 control chromosomes in the GnomAD database, including 137 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 0.024 (136 hom., cov: 34)
  • Exomes 𝑓: 0.0036 (1 hom.)
• Consequence: KDM8 ENST00000286096.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

KDM8 (HGNC:25840): (lysine demethylase 8) This gene likely encodes a histone lysine demethylase. Studies of a similar protein in mouse indicate a potential role for this protein as a tumor suppressor. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM8	NM_024773.3	c.-32+27G>A		intron_variant		ENST00000286096.9	NP_079049.2
KDM8	XM_017023676.2	c.-32+27G>A		intron_variant			XP_016879165.1
KDM8	XM_047434654.1	c.-32+27G>A		intron_variant			XP_047290610.1
KDM8	XM_047434655.1	c.-32+27G>A		intron_variant			XP_047290611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM8	ENST00000286096.9	c.-32+27G>A		intron_variant		1	NM_024773.3	ENSP00000286096	P1
KDM8	ENST00000564961.1	n.129+27G>A		intron_variant, non_coding_transcript_variant		1
KDM8	ENST00000562269.1	n.120+27G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3600 AN: 152236 Hom.: 134 Cov.: 34

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00361 AC: 45 AN: 12480 Hom.: 1 Cov.: 0 AF XY: 0.00232 AC XY: 16 AN XY: 6890

Gnomad4 AFR exome AF: 0.0674

Gnomad4 AMR exome AF: 0.00937

Gnomad4 ASJ exome AF: 0.00209

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000548

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0238 AC: 3620 AN: 152354 Hom.: 136 Cov.: 34 AF XY: 0.0229 AC XY: 1704 AN XY: 74500

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00684 Hom.: 13

Bravo AF: 0.0263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.2
DANN	Benign	0.87

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: rs16976587; hg19: chr16-27214984;