4-128857921-T-C

Position:

• chr4-128857921-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199320.4(JADE1):​c.981+467T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,004 control chromosomes in the GnomAD database, including 45,088 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (45088 hom., cov: 31)
• Consequence: JADE1 NM_199320.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE1	NM_199320.4	c.981+467T>C		intron_variant		ENST00000226319.11	NP_955352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE1	ENST00000226319.11	c.981+467T>C		intron_variant		5	NM_199320.4	ENSP00000226319.6

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114997 AN: 151886 Hom.: 45061 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.757 AC: 115084 AN: 152004 Hom.: 45088 Cov.: 31 AF XY: 0.762 AC XY: 56647 AN XY: 74292

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.764

Alfa AF: 0.831 Hom.: 70144

Bravo AF: 0.733

Asia WGS AF: 0.786 AC: 2733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2162126; hg19: chr4-129779076;