rs753842

Positions:

• chr19-4977733-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.-109+8503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,012 control chromosomes in the GnomAD database, including 6,316 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 0.25 (6316 hom., cov: 32)
• Consequence: KDM4B NM_015015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4B	NM_015015.3	c.-109+8503C>T		intron_variant		ENST00000159111.9	NP_055830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4B	ENST00000159111.9	c.-109+8503C>T		intron_variant		1	NM_015015.3	ENSP00000159111	P2
KDM4B	ENST00000381759.8	c.-109+8503C>T		intron_variant		1		ENSP00000371178
KDM4B	ENST00000588337.5	c.-26+8503C>T		intron_variant		5		ENSP00000468514
KDM4B	ENST00000611640.4	c.-109+8503C>T		intron_variant		5		ENSP00000480642	A2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38722 AN: 151894 Hom.: 6316 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38716 AN: 152012 Hom.: 6316 Cov.: 32 AF XY: 0.264 AC XY: 19617 AN XY: 74270

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.258

Alfa AF: 0.289 Hom.: 3143

Bravo AF: 0.236

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs753842; hg19: chr19-4977744;