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GeneBe

1-227733552-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_023007.3(JMJD4):c.684C>T(p.Tyr228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,606,598 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0085 ( 72 hom. )

Consequence

JMJD4
NM_023007.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.226
Variant links:
Genes affected
JMJD4 (HGNC:25724): (jumonji domain containing 4) Enables 2-oxoglutarate-dependent dioxygenase activity. Involved in positive regulation of translational termination and protein hydroxylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-227733552-G-A is Benign according to our data. Variant chr1-227733552-G-A is described in ClinVar as [Benign]. Clinvar id is 778255.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=-0.226 with no splicing effect.
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
JMJD4NM_023007.3 linkuse as main transcriptc.684C>T p.Tyr228= synonymous_variant 4/6 ENST00000620518.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JMJD4ENST00000620518.5 linkuse as main transcriptc.684C>T p.Tyr228= synonymous_variant 4/61 NM_023007.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00797
AC:
1213
AN:
152226
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00219
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.0124
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0252
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00930
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00895
AC:
2152
AN:
240360
Hom.:
20
AF XY:
0.00860
AC XY:
1127
AN XY:
130994
show subpopulations
Gnomad AFR exome
AF:
0.00245
Gnomad AMR exome
AF:
0.00876
Gnomad ASJ exome
AF:
0.00127
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.000332
Gnomad FIN exome
AF:
0.0261
Gnomad NFE exome
AF:
0.0110
Gnomad OTH exome
AF:
0.0123
GnomAD4 exome
AF:
0.00847
AC:
12321
AN:
1454254
Hom.:
72
Cov.:
32
AF XY:
0.00815
AC XY:
5899
AN XY:
723476
show subpopulations
Gnomad4 AFR exome
AF:
0.00176
Gnomad4 AMR exome
AF:
0.00858
Gnomad4 ASJ exome
AF:
0.000739
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000373
Gnomad4 FIN exome
AF:
0.0246
Gnomad4 NFE exome
AF:
0.00910
Gnomad4 OTH exome
AF:
0.00758
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00796
AC:
1213
AN:
152344
Hom.:
7
Cov.:
33
AF XY:
0.00855
AC XY:
637
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00219
Gnomad4 AMR
AF:
0.0124
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.0252
Gnomad4 NFE
AF:
0.00930
Gnomad4 OTH
AF:
0.00803
Alfa
AF:
0.00759
Hom.:
1
Bravo
AF:
0.00615
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00774
EpiControl
AF:
0.00945

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 testingInvitaeFeb 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
2.5
Dann
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs150323583; hg19: chr1-227921253; COSMIC: COSV100248096; COSMIC: COSV100248096; API