6-18197201-G-C

Variant names:

• chr6-18197201-G-C
• rs147829792
• NM_001364614.2:c.1114G>C

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.1114G>C​(p.Asp372His) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. D372N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• 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=0.26119715).

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.1114G>C	p.Asp372His	missense	Exon 11 of 22	NP_001351543.1	Q8NB78-1
	KDM1B	NM_001439117.1		c.1141G>C	p.Asp381His	missense	Exon 12 of 23	NP_001426046.1
	KDM1B	NM_001439118.1		c.1141G>C	p.Asp381His	missense	Exon 12 of 23	NP_001426047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	ENST00000650836.2	MANE Select	c.1114G>C	p.Asp372His	missense	Exon 11 of 22	ENSP00000499208.1	Q8NB78-1
	KDM1B	ENST00000546309.6	TSL:1	c.-18-17806G>C		intron	N/A	ENSP00000442670.1	Q08EI0
	KDM1B	ENST00000449850.2	TSL:5	c.1114G>C	p.Asp372His	missense	Exon 11 of 22	ENSP00000405669.2	H0Y6H0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727180

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

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PhyloP100		5.6
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.10
Sift	Benign	0.072	T
Sift4G	Benign	0.12	T
Vest4		0.60
MutPred		0.48		Gain of sheet (P = 0.0049)
MVP		0.14
MPC		0.40
ClinPred		0.68	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.62
Mutation Taster		=63/37	polymorphism

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: rs147829792; hg19: chr6-18197432;