chr6-18161343-C-G

Variant names:

• chr6-18161343-C-G
• rs115866051
• NM_001364614.2:c.104C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/21 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 Likely 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364614.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	NM_001364614.2	MANE Select	c.104C>G	p.Thr35Arg	missense	Exon 4 of 22	NP_001351543.1	Q8NB78-1
	KDM1B	NM_001439117.1		c.104C>G	p.Thr35Arg	missense	Exon 4 of 23	NP_001426046.1
	KDM1B	NM_001439118.1		c.104C>G	p.Thr35Arg	missense	Exon 4 of 23	NP_001426047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	ENST00000650836.2	MANE Select	c.104C>G	p.Thr35Arg	missense	Exon 4 of 22	ENSP00000499208.1	Q8NB78-1
	KDM1B	ENST00000546309.6	TSL:1	c.-19+5930C>G		intron	N/A	ENSP00000442670.1	Q08EI0
	KDM1B	ENST00000449850.2	TSL:5	c.104C>G	p.Thr35Arg	missense	Exon 4 of 22	ENSP00000405669.2	H0Y6H0

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.9
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)
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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs115866051; hg19: chr6-18161574;