1-202747003-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.2017-680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,048 control chromosomes in the GnomAD database, including 37,041 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 0.67 (37041 hom., cov: 32)
• Consequence: KDM5B NM_006618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5B	NM_006618.5	c.2017-680G>A		intron_variant		ENST00000367265.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5B	ENST00000367265.9	c.2017-680G>A		intron_variant		1	NM_006618.5	P4

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102257 AN: 151930 Hom.: 37035 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.673 AC: 102299 AN: 152048 Hom.: 37041 Cov.: 32 AF XY: 0.677 AC XY: 50345 AN XY: 74374

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.716

Alfa AF: 0.742 Hom.: 16920

Bravo AF: 0.662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.060
Dann	Benign	0.23

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: rs2363965; hg19: chr1-202716131;