rs169968

Variant names:

• chr6-18198064-T-G
• rs169968
• NM_001364614.2:c.1221+403T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	NM_001364614.2	MANE Select	c.1221+403T>G		intron	N/A	NP_001351543.1
	KDM1B	NM_001439117.1		c.1248+403T>G		intron	N/A	NP_001426046.1
	KDM1B	NM_001439118.1		c.1248+403T>G		intron	N/A	NP_001426047.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	ENST00000650836.2	MANE Select	c.1221+403T>G		intron	N/A	ENSP00000499208.1
	KDM1B	ENST00000546309.6	TSL:1	c.-18-16943T>G		intron	N/A	ENSP00000442670.1
	KDM1B	ENST00000449850.2	TSL:5	c.1221+403T>G		intron	N/A	ENSP00000405669.2

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

African (AFR) AF: 0.0560 AC: 2314 AN: 41354

American (AMR) AF: 0.0901 AC: 1367 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.0744 AC: 382 AN: 5136

South Asian (SAS) AF: 0.220 AC: 1055 AN: 4806

European-Finnish (FIN) AF: 0.0573 AC: 604 AN: 10536

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4803 AN: 67938

Other (OTH) AF: 0.0846 AC: 178 AN: 2104

Alfa AF: 0.0721 Hom.: 60

Bravo AF: 0.0703

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.86
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs169968; hg19: chr6-18198295;