chr6-18187685-C-T

Variant names:

• chr6-18187685-C-T
• rs372534
• NM_001364614.2:c.574-107C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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.574-107C>T		intron	N/A	NP_001351543.1
	KDM1B	NM_001439117.1		c.601-107C>T		intron	N/A	NP_001426046.1
	KDM1B	NM_001439118.1		c.601-107C>T		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.574-107C>T		intron	N/A	ENSP00000499208.1
	KDM1B	ENST00000546309.6	TSL:1	c.-18-27322C>T		intron	N/A	ENSP00000442670.1
	KDM1B	ENST00000449850.2	TSL:5	c.574-107C>T		intron	N/A	ENSP00000405669.2

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

African (AFR) AF: 0.966 AC: 15390 AN: 15934

American (AMR) AF: 0.912 AC: 28080 AN: 30784

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 14195 AN: 17014

East Asian (EAS) AF: 0.642 AC: 20298 AN: 31640

South Asian (SAS) AF: 0.825 AC: 45216 AN: 54820

European-Finnish (FIN) AF: 0.800 AC: 27233 AN: 34024

Middle Eastern (MID) AF: 0.812 AC: 3105 AN: 3826

European-Non Finnish (NFE) AF: 0.809 AC: 286770 AN: 354296

Other (OTH) AF: 0.820 AC: 25142 AN: 30666

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

African (AFR) AF: 0.964 AC: 40011 AN: 41518

American (AMR) AF: 0.888 AC: 13581 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2877 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3324 AN: 5140

South Asian (SAS) AF: 0.827 AC: 3987 AN: 4820

European-Finnish (FIN) AF: 0.798 AC: 8455 AN: 10594

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55156 AN: 68012

Other (OTH) AF: 0.850 AC: 1797 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.66
PhyloP100		-0.92
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: rs372534; hg19: chr6-18187916;