Genetic Variant NM_199320.4:c.1899A>G (chr4-128871632-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_199320.4(JADE1):c.1899A>G(p.Leu633Leu) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0700

Publications

3 publications found

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]

JADE1 links:

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]

SCLT1 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
Bardet-Biedl syndrome
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P
Senior-Loken syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SCLT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 4-128871632-A-G is Benign according to our data. Variant chr4-128871632-A-G is described in ClinVar as Benign. ClinVar VariationId is 776018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199320.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JADE1	NM_199320.4	MANE Select	c.1899A>G	p.Leu633Leu	synonymous	Exon 11 of 11	NP_955352.1	Q6IE81-1
JADE1	NM_001287439.2		c.1899A>G	p.Leu633Leu	synonymous	Exon 11 of 11	NP_001274368.1	Q6IE81-1
JADE1	NM_001287440.2		c.1899A>G	p.Leu633Leu	synonymous	Exon 11 of 11	NP_001274369.1	Q6IE81-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JADE1	ENST00000226319.11	TSL:5 MANE Select	c.1899A>G	p.Leu633Leu	synonymous	Exon 11 of 11	ENSP00000226319.6	Q6IE81-1
JADE1	ENST00000947587.1		c.1998A>G	p.Leu666Leu	synonymous	Exon 11 of 11	ENSP00000617646.1
JADE1	ENST00000887597.1		c.1971A>G	p.Leu657Leu	synonymous	Exon 12 of 12	ENSP00000557656.1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3388

AN:

152206

Hom.:

110

Cov.:

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

GnomAD2 exomes

AF:

0.00655

AC:

1643

AN:

250830

AF XY:

0.00527

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 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.:

AF XY:

0.00303

AC XY:

2207

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0774

AC:

2590

AN:

33480

American (AMR)

AF:

0.00465

AC:

208

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.00618

AC:

533

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000744

AC:

827

AN:

1112000

Other (OTH)

AF:

0.00667

AC:

403

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

308

616

923

1231

1539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0224

AC:

3405

AN:

152324

Hom.:

111

Cov.:

AF XY:

0.0220

AC XY:

1637

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0736

AC:

3060

AN:

41556

American (AMR)

AF:

0.0124

AC:

189

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00786

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68040

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

162

323

485

646

808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.0140

AC:

AN:

3476

EpiCase

AF:

0.00142

EpiControl

AF:

0.00136

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.37

(source)

DANN

Benign

0.53

PhyloP100

0.070

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over