rs169968

Positions:

• chr6-18198064-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364614.2(KDM1B):​c.1221+403T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 151,728 control chromosomes in the GnomAD database, including 483 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 0.073 (483 hom., cov: 30)
• Consequence: KDM1B NM_001364614.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM1B	NM_001364614.2	c.1221+403T>G		intron_variant		ENST00000650836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM1B	ENST00000650836.2	c.1221+403T>G		intron_variant			NM_001364614.2	P4
KDM1B	ENST00000546309.6	c.-18-16943T>G		intron_variant		1
KDM1B	ENST00000297792.9	c.825+403T>G		intron_variant		2
KDM1B	ENST00000449850.2	c.1221+403T>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11098 AN: 151608 Hom.: 482 Cov.: 30

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.0732 AC: 11107 AN: 151728 Hom.: 483 Cov.: 30 AF XY: 0.0758 AC XY: 5619 AN XY: 74148

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.0901

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.0744

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0707

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0725 Hom.: 58

Bravo AF: 0.0703

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs169968; hg19: chr6-18198295;