chr6-18208189-G-A

Position:

• chr6-18208189-G-A

Variant summary

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

The NM_001364614.2(KDM1B):​c.1849G>A​(p.Gly617Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

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=0.0828788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM1B	NM_001364614.2	c.1849G>A	p.Gly617Arg	missense_variant	17/22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM1B	ENST00000650836.2	c.1849G>A	p.Gly617Arg	missense_variant	17/22		NM_001364614.2	ENSP00000499208.1
KDM1B	ENST00000546309.6	c.-18-6818G>A		intron_variant		1		ENSP00000442670.1
KDM1B	ENST00000449850.2	c.1852G>A	p.Gly618Arg	missense_variant	17/22	5		ENSP00000405669.2
KDM1B	ENST00000297792.9	c.1153G>A	p.Gly385Arg	missense_variant	13/18	2		ENSP00000297792.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461160 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726942

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: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.1153G>A (p.G385R) alteration is located in exon 13 (coding exon 11) of the KDM1B gene. This alteration results from a G to A substitution at nucleotide position 1153, causing the glycine (G) at amino acid position 385 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	0.0082	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.57
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.67	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.3	.;N
REVEL	Benign	0.17
Sift	Benign	0.50	.;T
Sift4G	Benign	0.53	.;T
Vest4		0.13
MVP		0.73
MPC		0.40
ClinPred		0.12	T
GERP RS		2.4
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 1

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: chr6-18208420;