1-202729821-ACG-CAA

Variant names:

• chr1-202729821-ACG-CAA
• NM_006618.5:c.4381_4383delCGTinsTTG
• KDM5B p.Arg1461Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006618.5(KDM5B):​c.4381_4383delCGTinsTTG​(p.Arg1461Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1461H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM5B NM_006618.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

Genes affected

KDM5B (HGNC:18039): (lysine demethylase 5B) This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

KDM5B Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 65

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006618.5. 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
	KDM5B	NM_006618.5	MANE Select	c.4381_4383delCGTinsTTG	p.Arg1461Leu	missense	N/A	NP_006609.3
	KDM5B	NM_001314042.2		c.4489_4491delCGTinsTTG	p.Arg1497Leu	missense	N/A	NP_001300971.1	Q9UGL1-2
	KDM5B	NM_001399817.1		c.4366_4368delCGTinsTTG	p.Arg1456Leu	missense	N/A	NP_001386746.1	A0A3B3IS40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5B	ENST00000367265.9	TSL:1 MANE Select	c.4381_4383delCGTinsTTG	p.Arg1461Leu	missense	N/A	ENSP00000356234.3	Q9UGL1-1
	KDM5B	ENST00000367264.7	TSL:1	c.4489_4491delCGTinsTTG	p.Arg1497Leu	missense	N/A	ENSP00000356233.2	Q9UGL1-2
	KDM5B	ENST00000472822.6	TSL:1	n.1387_1389delCGTinsTTG		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-202698949;