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GeneBe

19-5041167-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015015.3(KDM4B):c.348T>C(p.Asp116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 1,612,104 control chromosomes in the GnomAD database, including 651,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.91 ( 63414 hom., cov: 32)
Exomes 𝑓: 0.90 ( 587680 hom. )

Consequence

KDM4B
NM_015015.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.52
Variant links:
Genes affected
KDM4B (HGNC:29136): (lysine demethylase 4B) Enables histone H3-methyl-lysine-36 demethylase activity and histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K36 demethylation and histone H3-K9 demethylation. Located in cytosol and nucleoplasm. Implicated in autosomal dominant non-syndromic intellectual disability; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-5041167-T-C is Benign according to our data. Variant chr19-5041167-T-C is described in ClinVar as [Benign]. Clinvar id is 1224153.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.52 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KDM4BNM_015015.3 linkuse as main transcriptc.348T>C p.Asp116= synonymous_variant 5/23 ENST00000159111.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KDM4BENST00000159111.9 linkuse as main transcriptc.348T>C p.Asp116= synonymous_variant 5/231 NM_015015.3 P2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.911
AC:
138542
AN:
152096
Hom.:
63354
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.974
Gnomad AMI
AF:
0.934
Gnomad AMR
AF:
0.816
Gnomad ASJ
AF:
0.891
Gnomad EAS
AF:
0.756
Gnomad SAS
AF:
0.869
Gnomad FIN
AF:
0.918
Gnomad MID
AF:
0.899
Gnomad NFE
AF:
0.908
Gnomad OTH
AF:
0.910
GnomAD3 exomes
AF:
0.871
AC:
218855
AN:
251348
Hom.:
96040
AF XY:
0.875
AC XY:
118819
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.976
Gnomad AMR exome
AF:
0.737
Gnomad ASJ exome
AF:
0.895
Gnomad EAS exome
AF:
0.741
Gnomad SAS exome
AF:
0.866
Gnomad FIN exome
AF:
0.912
Gnomad NFE exome
AF:
0.908
Gnomad OTH exome
AF:
0.881
GnomAD4 exome
AF:
0.896
AC:
1308275
AN:
1459890
Hom.:
587680
Cov.:
39
AF XY:
0.895
AC XY:
650111
AN XY:
726292
show subpopulations
Gnomad4 AFR exome
AF:
0.979
Gnomad4 AMR exome
AF:
0.746
Gnomad4 ASJ exome
AF:
0.898
Gnomad4 EAS exome
AF:
0.768
Gnomad4 SAS exome
AF:
0.864
Gnomad4 FIN exome
AF:
0.913
Gnomad4 NFE exome
AF:
0.906
Gnomad4 OTH exome
AF:
0.891
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.911
AC:
138654
AN:
152214
Hom.:
63414
Cov.:
32
AF XY:
0.909
AC XY:
67636
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.974
Gnomad4 AMR
AF:
0.816
Gnomad4 ASJ
AF:
0.891
Gnomad4 EAS
AF:
0.755
Gnomad4 SAS
AF:
0.868
Gnomad4 FIN
AF:
0.918
Gnomad4 NFE
AF:
0.908
Gnomad4 OTH
AF:
0.911
Alfa
AF:
0.903
Hom.:
82050
Bravo
AF:
0.904
Asia WGS
AF:
0.837
AC:
2913
AN:
3478
EpiCase
AF:
0.898
EpiControl
AF:
0.898

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 17, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
0.18
Dann
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs2240678; hg19: chr19-5041178; COSMIC: COSV50211732; API