4-128857921-T-C

Variant names:

• chr4-128857921-T-C
• rs2162126
• NM_199320.4:c.981+467T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE1	NM_199320.4	MANE Select	c.981+467T>C		intron	N/A	NP_955352.1
	JADE1	NM_001287439.2		c.981+467T>C		intron	N/A	NP_001274368.1
	JADE1	NM_001287440.2		c.981+467T>C		intron	N/A	NP_001274369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE1	ENST00000226319.11	TSL:5 MANE Select	c.981+467T>C		intron	N/A	ENSP00000226319.6
	JADE1	ENST00000413543.6	TSL:1	c.981+467T>C		intron	N/A	ENSP00000404211.2
	JADE1	ENST00000511647.5	TSL:1	c.981+467T>C		intron	N/A	ENSP00000423737.1

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

African (AFR) AF: 0.539 AC: 22333 AN: 41410

American (AMR) AF: 0.779 AC: 11904 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2913 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3797 AN: 5150

South Asian (SAS) AF: 0.914 AC: 4393 AN: 4808

European-Finnish (FIN) AF: 0.885 AC: 9359 AN: 10572

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57874 AN: 67992

Other (OTH) AF: 0.764 AC: 1613 AN: 2110

Alfa AF: 0.802 Hom.: 95672

Bravo AF: 0.733

Asia WGS AF: 0.786 AC: 2733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.34
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2162126; hg19: chr4-129779076;