19-5080636-C-T

Variant summary

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

The NM_015015.3(KDM4B):c.781-1731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,276 control chromosomes in the GnomAD database, including 894 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 0.093 (893 hom., cov: 33)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: KDM4B NM_015015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58

Genes affected

KDM4B (HGNC:29136): (lysine demethylase 4B) Enables histone H3-methyl-lysine-36 demethylase activity and histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K36 demethylation and histone H3-K9 demethylation. Located in cytosol and nucleoplasm. Implicated in autosomal dominant non-syndromic intellectual disability; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4B	NM_015015.3	c.781-1731C>T		intron_variant		ENST00000159111.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4B	ENST00000159111.9	c.781-1731C>T		intron_variant		1	NM_015015.3	P2

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14132 AN: 152140 Hom.: 886 Cov.: 33

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.222 AC: 4 AN: 18 Hom.: 1 AF XY: 0.250 AC XY: 4 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0929 AC: 14143 AN: 152258 Hom.: 893 Cov.: 33 AF XY: 0.0951 AC XY: 7077 AN XY: 74442

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0845

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.0893

Alfa AF: 0.0717 Hom.: 342

Bravo AF: 0.0999

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.040
Dann	Benign	0.58

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: rs11673509; hg19: chr19-5080647;