Menu
GeneBe

4-128871632-A-G

Variant summary

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

The NM_199320.4(JADE1):c.1899A>G(p.Leu633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,614,198 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 111 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 113 hom. )

Consequence

JADE1
NM_199320.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0700
Variant links:
Genes affected
JADE1 (HGNC:30027): (jade family PHD finger 1) Enables transcription coactivator activity. Involved in histone acetylation and negative regulation of canonical Wnt signaling pathway. Acts upstream of or within negative regulation of G1/S transition of mitotic cell cycle. Located in several cellular components, including ciliary basal body; cytosol; and nuclear speck. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]
SCLT1 (HGNC:26406): (sodium channel and clathrin linker 1) This gene encodes an adaptor protein. Studies of a related gene in rat suggest that the encoded protein functions to link clathrin to the sodium channel protein type 10 subunit alpha protein. The encoded protein has also been identified as a component of distal appendages of centrioles that is necessary for ciliogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

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=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-128871632-A-G is Benign according to our data. Variant chr4-128871632-A-G is described in ClinVar as [Benign]. Clinvar id is 776018.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=0.07 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 = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JADE1NM_199320.4 linkuse as main transcriptc.1899A>G p.Leu633= synonymous_variant 11/11 ENST00000226319.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JADE1ENST00000226319.11 linkuse as main transcriptc.1899A>G p.Leu633= synonymous_variant 11/115 NM_199320.4 P1Q6IE81-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0223
AC:
3388
AN:
152206
Hom.:
110
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0734
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00785
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00106
Gnomad OTH
AF:
0.0201
GnomAD3 exomes
AF:
0.00655
AC:
1643
AN:
250830
Hom.:
53
AF XY:
0.00527
AC XY:
714
AN XY:
135540
show subpopulations
Gnomad AFR exome
AF:
0.0735
Gnomad AMR exome
AF:
0.00399
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00614
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000883
Gnomad OTH exome
AF:
0.00360
GnomAD4 exome
AF:
0.00316
AC:
4614
AN:
1461874
Hom.:
113
Cov.:
32
AF XY:
0.00303
AC XY:
2207
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0774
Gnomad4 AMR exome
AF:
0.00465
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00618
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000744
Gnomad4 OTH exome
AF:
0.00667
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0224
AC:
3405
AN:
152324
Hom.:
111
Cov.:
32
AF XY:
0.0220
AC XY:
1637
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0736
Gnomad4 AMR
AF:
0.0124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00786
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00106
Gnomad4 OTH
AF:
0.0203
Alfa
AF:
0.0115
Hom.:
22
Bravo
AF:
0.0249
Asia WGS
AF:
0.0140
AC:
48
AN:
3476
EpiCase
AF:
0.00142
EpiControl
AF:
0.00136

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 testingInvitaeJun 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.37
Dann
Benign
0.53

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: rs6850940; hg19: chr4-129792787; API