Variant 4-128861698-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_199320.4(JADE1):c.982-6T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,668 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 89 hom. )

Consequence

JADE1
NM_199320.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001185

Clinical Significance

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

Conservation

PhyloP100: -1.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-128861698-T-C is Benign according to our data. Variant chr4-128861698-T-C is described in ClinVar as [Benign]. Clinvar id is 778861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00366 (557/152354) while in subpopulation EAS AF= 0.0409 (212/5188). AF 95% confidence interval is 0.0364. There are 9 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 557 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE1	NM_199320.4 linkuse as main transcript	c.982-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000226319.11	NP_955352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE1	ENST00000226319.11 linkuse as main transcript	c.982-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_199320.4	ENSP00000226319	P1	Q6IE81-1

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0408

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00978

AC:

2449

AN:

250318

Hom.:

AF XY:

0.00827

AC XY:

1119

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0445

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0444

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00224

AC:

3268

AN:

1461314

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1477

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0278

Gnomad4 SAS exome

AF:

0.000917

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000837

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.00366

AC:

557

AN:

152354

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.0193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0409

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000926

Hom.:

Bravo

AF:

0.00665

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over