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GeneBe

9-6849518-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015061.6(KDM4C):c.447A>G(p.Glu149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 1,574,234 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 10 hom. )

Consequence

KDM4C
NM_015061.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74
Variant links:
Genes affected
KDM4C (HGNC:17071): (lysine demethylase 4C) This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

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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=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-6849518-A-G is Benign according to our data. Variant chr9-6849518-A-G is described in ClinVar as [Benign]. Clinvar id is 714419.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=1.74 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00544 (828/152158) while in subpopulation AFR AF= 0.0191 (793/41512). AF 95% confidence interval is 0.018. There are 9 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KDM4CNM_015061.6 linkuse as main transcriptc.447A>G p.Glu149= synonymous_variant 5/22 ENST00000381309.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KDM4CENST00000381309.8 linkuse as main transcriptc.447A>G p.Glu149= synonymous_variant 5/221 NM_015061.6 P1Q9H3R0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00538
AC:
818
AN:
152040
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0189
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00131
AC:
319
AN:
244036
Hom.:
1
AF XY:
0.000956
AC XY:
126
AN XY:
131790
show subpopulations
Gnomad AFR exome
AF:
0.0178
Gnomad AMR exome
AF:
0.000798
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000701
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000897
Gnomad OTH exome
AF:
0.000675
GnomAD4 exome
AF:
0.000514
AC:
731
AN:
1422076
Hom.:
10
Cov.:
31
AF XY:
0.000404
AC XY:
283
AN XY:
701050
show subpopulations
Gnomad4 AFR exome
AF:
0.0184
Gnomad4 AMR exome
AF:
0.000987
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000373
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000461
Gnomad4 OTH exome
AF:
0.00130
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00544
AC:
828
AN:
152158
Hom.:
9
Cov.:
32
AF XY:
0.00520
AC XY:
387
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0191
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00235
Hom.:
3
Bravo
AF:
0.00590
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

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 testingInvitaeApr 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
5.5
Dann
Benign
0.50
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

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: rs61750314; hg19: chr9-6849518; COSMIC: COSV101185264; API