1-202727750-C-T

Variant names:

• chr1-202727750-C-T
• rs10494836
• ENST00000472822.6:n.3460G>A

Variant summary

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

The ENST00000472822.6(KDM5B):​n.3460G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 152,692 control chromosomes in the GnomAD database, including 451 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 0.059 (451 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (0 hom.)
• Consequence: KDM5B ENST00000472822.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472822.6. 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
	KDM5B	NM_006618.5	MANE Select	c.*1286G>A		3_prime_UTR	Exon 27 of 27	NP_006609.3
	KDM5B	NM_001314042.2		c.*1286G>A		3_prime_UTR	Exon 28 of 28	NP_001300971.1
	KDM5B	NM_001399817.1		c.*1286G>A		3_prime_UTR	Exon 27 of 27	NP_001386746.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5B	ENST00000472822.6	TSL:1	n.3460G>A		non_coding_transcript_exon	Exon 4 of 4
	KDM5B	ENST00000367265.9	TSL:1 MANE Select	c.*1286G>A		3_prime_UTR	Exon 27 of 27	ENSP00000356234.3
	KDM5B	ENST00000367264.7	TSL:1	c.*1286G>A		3_prime_UTR	Exon 28 of 28	ENSP00000356233.2

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8932 AN: 152126 Hom.: 452 Cov.: 33

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.00893 AC: 4 AN: 448 Hom.: 0 Cov.: 0 AF XY: 0.00735 AC XY: 2 AN XY: 272

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00935 AC: 4 AN: 428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0588 AC: 8948 AN: 152244 Hom.: 451 Cov.: 33 AF XY: 0.0605 AC XY: 4503 AN XY: 74438

African (AFR) AF: 0.0676 AC: 2808 AN: 41546

American (AMR) AF: 0.129 AC: 1976 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5168

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4826

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0329 AC: 2235 AN: 68010

Other (OTH) AF: 0.0497 AC: 105 AN: 2114

Alfa AF: 0.0422 Hom.: 295

Bravo AF: 0.0716

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10494836; hg19: chr1-202696878;