rs776466616

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_006618.5(KDM5B):​c.4426G>T​(p.Glu1476*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KDM5B
NM_006618.5 stop_gained

Scores

4
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.06
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0451 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM5BNM_006618.5 linkc.4426G>T p.Glu1476* stop_gained Exon 26 of 27 ENST00000367265.9 NP_006609.3 Q9UGL1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM5BENST00000367265.9 linkc.4426G>T p.Glu1476* stop_gained Exon 26 of 27 1 NM_006618.5 ENSP00000356234.3 Q9UGL1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251370
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461686
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
39
DANN
Uncertain
1.0
Eigen
Pathogenic
0.80
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.77
GERP RS
5.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.24
Position offset: -6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776466616; hg19: chr1-202698906; API