chr6-18163842-T-C

Variant names:

• chr6-18163842-T-C
• rs9396834
• NM_001364614.2:c.305+918T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364614.2(KDM1B):​c.305+918T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,018 control chromosomes in the GnomAD database, including 9,063 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 0.34 (9063 hom., cov: 33)
• Consequence: KDM1B NM_001364614.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1B	NM_001364614.2	c.305+918T>C		intron_variant	Intron 5 of 21	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1B	ENST00000650836.2	c.305+918T>C		intron_variant	Intron 5 of 21		NM_001364614.2	ENSP00000499208.1
KDM1B	ENST00000546309.6	c.-19+8429T>C		intron_variant	Intron 1 of 3	1		ENSP00000442670.1
KDM1B	ENST00000449850.2	c.305+918T>C		intron_variant	Intron 5 of 21	5		ENSP00000405669.2
KDM1B	ENST00000297792.9	c.305+918T>C		intron_variant	Intron 5 of 17	2		ENSP00000297792.5

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52056 AN: 151900 Hom.: 9061 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.343 AC: 52073 AN: 152018 Hom.: 9063 Cov.: 33 AF XY: 0.342 AC XY: 25400 AN XY: 74314

African (AFR) AF: 0.290 AC: 12038 AN: 41470

American (AMR) AF: 0.326 AC: 4968 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2698 AN: 5168

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4110 AN: 10552

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24463 AN: 67972

Other (OTH) AF: 0.340 AC: 717 AN: 2108

Alfa AF: 0.355 Hom.: 30430

Bravo AF: 0.339

Asia WGS AF: 0.366 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.48
PhyloP100		-1.3
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: rs9396834; hg19: chr6-18164073;