4-128861698-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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, single submitter B:1
• Conservation: PhyloP100: -1.42

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 552 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 552 AN: 152236 Hom.: 8 Cov.: 32

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.: 75 AF XY: 0.00827 AC XY: 1119 AN XY: 135332

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.: 89 Cov.: 31 AF XY: 0.00203 AC XY: 1477 AN XY: 726938

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.: 9 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74506

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.: 1

Bravo AF: 0.00665

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

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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

Other links and lift over

dbSNP: rs113154795; hg19: chr4-129782853;