6-18187685-C-T

Position:

• chr6-18187685-C-T

Variant summary

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

The NM_001364614.2(KDM1B):​c.574-107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 725,170 control chromosomes in the GnomAD database, including 246,430 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 0.86 (56269 hom., cov: 31)
  • Exomes 𝑓: 0.81 (190161 hom.)
• Consequence: KDM1B NM_001364614.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM1B	NM_001364614.2	c.574-107C>T		intron_variant		ENST00000650836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM1B	ENST00000650836.2	c.574-107C>T		intron_variant			NM_001364614.2	P4
KDM1B	ENST00000546309.6	c.-18-27322C>T		intron_variant		1
KDM1B	ENST00000297792.9	c.573+1875C>T		intron_variant		2
KDM1B	ENST00000449850.2	c.574-107C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130106 AN: 152048 Hom.: 56208 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.812 AC: 465429 AN: 573004 Hom.: 190161 AF XY: 0.810 AC XY: 242896 AN XY: 299830

Gnomad4 AFR exome AF: 0.966

Gnomad4 AMR exome AF: 0.912

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.825

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.856 AC: 130227 AN: 152166 Hom.: 56269 Cov.: 31 AF XY: 0.854 AC XY: 63498 AN XY: 74392

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.850

Alfa AF: 0.843 Hom.: 8572

Bravo AF: 0.867

Asia WGS AF: 0.766 AC: 2662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.66

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: rs372534; hg19: chr6-18187916;