1-202727750-C-T

Position:

• chr1-202727750-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006618.5(KDM5B):​c.*1286G>A variant causes a 3 prime UTR 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 NM_006618.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5B	NM_006618.5	c.*1286G>A		3_prime_UTR_variant	27/27	ENST00000367265.9	NP_006609.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM5B	ENST00000367265.9	c.*1286G>A		3_prime_UTR_variant	27/27	1	NM_006618.5	ENSP00000356234	P4

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

Gnomad4 FIN exome AF: 0.00935

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0329

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0374 Hom.: 200

Bravo AF: 0.0716

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494836; hg19: chr1-202696878;