rs115866051

Variant names:

• chr6-18161343-C-G
• NM_001364614.2:c.104C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-18161343-C-G
• chr6-18161343-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364614.2(KDM1B):​c.104C>G​(p.Thr35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T35I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

Genes affected

KDM1B (HGNC:21577): (lysine demethylase 1B) Flavin-dependent histone demethylases, such as KDM1B, regulate histone lysine methylation, an epigenetic mark that regulates gene expression and chromatin function (Karytinos et al., 2009 [PubMed 19407342]).[supplied by OMIM, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08845949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1B	NM_001364614.2	c.104C>G	p.Thr35Arg	missense_variant	Exon 4 of 22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1B	ENST00000650836.2	c.104C>G	p.Thr35Arg	missense_variant	Exon 4 of 22		NM_001364614.2	ENSP00000499208.1
KDM1B	ENST00000546309.6	c.-19+5930C>G		intron_variant	Intron 1 of 3	1		ENSP00000442670.1
KDM1B	ENST00000449850.2	c.104C>G	p.Thr35Arg	missense_variant	Exon 4 of 22	5		ENSP00000405669.2
KDM1B	ENST00000297792.9	c.104C>G	p.Thr35Arg	missense_variant	Exon 4 of 18	2		ENSP00000297792.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.97
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.52	.;N
REVEL	Benign	0.060
Sift	Benign	0.031	.;D
Sift4G	Uncertain	0.045	.;D
Vest4		0.17
MutPred		0.15		Loss of phosphorylation at T35 (P = 0.0062);Loss of phosphorylation at T35 (P = 0.0062);
MVP		0.093
MPC		1.1
ClinPred		0.57	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-18161574;