chr19-5081168-T-C

Position:

• chr19-5081168-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
KDM4B	NM_015015.3	c.781-1199T>C		intron_variant		ENST00000159111.9	NP_055830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4B	ENST00000159111.9	c.781-1199T>C		intron_variant		1	NM_015015.3	ENSP00000159111	P2

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

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0569

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.111

Alfa AF: 0.131 Hom.: 1842

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs4807685; hg19: chr19-5081179;