6-18161343-C-T

Variant names:

• chr6-18161343-C-T
• rs115866051
• NM_001364614.2:c.104C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.87
• Publications: 6 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 -20 ACMG points.

• 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/Likely_benign. ClinVar VariationId is 784064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	NM_001364614.2	MANE Select	c.104C>T	p.Thr35Ile	missense	Exon 4 of 22	NP_001351543.1	Q8NB78-1
	KDM1B	NM_001439117.1		c.104C>T	p.Thr35Ile	missense	Exon 4 of 23	NP_001426046.1
	KDM1B	NM_001439118.1		c.104C>T	p.Thr35Ile	missense	Exon 4 of 23	NP_001426047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	ENST00000650836.2	MANE Select	c.104C>T	p.Thr35Ile	missense	Exon 4 of 22	ENSP00000499208.1	Q8NB78-1
	KDM1B	ENST00000546309.6	TSL:1	c.-19+5930C>T		intron	N/A	ENSP00000442670.1	Q08EI0
	KDM1B	ENST00000449850.2	TSL:5	c.104C>T	p.Thr35Ile	missense	Exon 4 of 22	ENSP00000405669.2	H0Y6H0

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

GnomAD2 exomes AF: 0.00247 AC: 620 AN: 251400 AF XY: 0.00177

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 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

African (AFR) AF: 0.0334 AC: 1119 AN: 33472

American (AMR) AF: 0.00239 AC: 107 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.000308 AC: 342 AN: 1111900

Other (OTH) AF: 0.00280 AC: 169 AN: 60380

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

African (AFR) AF: 0.0308 AC: 1276 AN: 41488

American (AMR) AF: 0.00432 AC: 66 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68020

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00640 Hom.: 9

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.074
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.044	D
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs115866051; hg19: chr6-18161574;