11-94991836-A-G

Variant names:

• chr11-94991836-A-G
• rs1385967
• NM_018039.3:c.-349-5188A>G

Variant summary

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

The NM_018039.3(KDM4D):​c.-349-5188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,210 control chromosomes in the GnomAD database, including 16,760 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 0.46 (16760 hom., cov: 30)
• Consequence: KDM4D NM_018039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 1 publications found

Genes affected

KDM4D (HGNC:25498): (lysine demethylase 4D) Enables histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K9 demethylation. Acts upstream of or within several processes, including cellular response to ionizing radiation; positive regulation of chromatin binding activity; and positive regulation of double-strand break repair via nonhomologous end joining. Located in site of double-strand break. Biomarker of nephroblastoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299693 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4D	NM_018039.3	c.-349-5188A>G		intron_variant	Intron 2 of 2	ENST00000335080.6	NP_060509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4D	ENST00000335080.6	c.-349-5188A>G		intron_variant	Intron 2 of 2	1	NM_018039.3	ENSP00000334181.5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70045 AN: 151094 Hom.: 16757 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.463 AC: 70055 AN: 151210 Hom.: 16760 Cov.: 30 AF XY: 0.461 AC XY: 34074 AN XY: 73880

African (AFR) AF: 0.376 AC: 15542 AN: 41358

American (AMR) AF: 0.444 AC: 6760 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1218 AN: 5156

South Asian (SAS) AF: 0.425 AC: 2043 AN: 4810

European-Finnish (FIN) AF: 0.510 AC: 5187 AN: 10164

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.530 AC: 35874 AN: 67726

Other (OTH) AF: 0.479 AC: 1003 AN: 2094

Alfa AF: 0.513 Hom.: 11951

Bravo AF: 0.453

Asia WGS AF: 0.323 AC: 1124 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.27
PhyloP100		0.19
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: rs1385967; hg19: chr11-94725000;