rs4807685

Variant names:

• chr19-5081168-T-C
• rs4807685
• NM_015015.3:c.781-1199T>C

Variant summary

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

The NM_015015.3(KDM4B):​c.781-1199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,222 control chromosomes in the GnomAD database, including 884 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 0.095 (884 hom., cov: 33)
• Consequence: KDM4B NM_015015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 6 publications found

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]

KDM4B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Illumina
• intellectual developmental disorder, autosomal dominant 65

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4B	NM_015015.3	c.781-1199T>C		intron_variant	Intron 8 of 22	ENST00000159111.9	NP_055830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4B	ENST00000159111.9	c.781-1199T>C		intron_variant	Intron 8 of 22	1	NM_015015.3	ENSP00000159111.3

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14414 AN: 152104 Hom.: 884 Cov.: 33

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0947 AC: 14411 AN: 152222 Hom.: 884 Cov.: 33 AF XY: 0.0909 AC XY: 6763 AN XY: 74428

African (AFR) AF: 0.0301 AC: 1252 AN: 41530

American (AMR) AF: 0.149 AC: 2280 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0569 AC: 274 AN: 4814

European-Finnish (FIN) AF: 0.0668 AC: 709 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8923 AN: 67982

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.129 Hom.: 2146

Bravo AF: 0.0985

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.25
DANN	Benign	0.17
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs4807685; hg19: chr19-5081179;