6-18161343-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

The NM_001364614.2(KDM1B):c.104C>T(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,848 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (19 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (22 hom.)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87

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 -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, KDM1B
• BP4: Computational evidence support a benign effect (MetaRNN=0.0032545626).
• BP6: Variant 6-18161343-C-T is Benign according to our data. Variant chr6-18161343-C-T is described in ClinVar as [Benign]. Clinvar id is 784064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.009 (1370/152150) while in subpopulation AFR AF= 0.0308 (1276/41488). AF 95% confidence interval is 0.0294. There are 19 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM1B	NM_001364614.2	c.104C>T	p.Thr35Ile	missense_variant	4/22	ENST00000650836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM1B	ENST00000650836.2	c.104C>T	p.Thr35Ile	missense_variant	4/22		NM_001364614.2	P4
KDM1B	ENST00000546309.6	c.-19+5930C>T		intron_variant		1
KDM1B	ENST00000449850.2	c.104C>T	p.Thr35Ile	missense_variant	4/22	5		A1
KDM1B	ENST00000297792.9	c.104C>T	p.Thr35Ile	missense_variant	4/18	2

Frequencies

GnomAD3 genomes AF: 0.00898 AC: 1366 AN: 152032 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00247 AC: 620 AN: 251400 Hom.: 10 AF XY: 0.00177 AC XY: 241 AN XY: 135888

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00123 AC: 1791 AN: 1461698 Hom.: 22 Cov.: 31 AF XY: 0.00112 AC XY: 811 AN XY: 727156

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.00239

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000308

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00900 AC: 1370 AN: 152150 Hom.: 19 Cov.: 31 AF XY: 0.00863 AC XY: 642 AN XY: 74370

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.00432

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00358 Hom.: 2

Bravo AF: 0.0104

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0277 AC: 122

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00306 AC: 371

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Uncertain	0.99
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	D;D
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.39	T
Vest4		0.071
MVP		0.043
MPC		0.70
ClinPred		0.015	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs115866051; hg19: chr6-18161574;