14-75433818-A-G

Variant names:

• chr14-75433818-A-G
• rs715463
• NM_001135048.2:c.-23-4080A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135048.2(JDP2):​c.-23-4080A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,748 control chromosomes in the GnomAD database, including 13,079 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 0.39 (13079 hom., cov: 30)
• Consequence: JDP2 NM_001135048.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 6 publications found

Genes affected

JDP2 (HGNC:17546): (Jun dimerization protein 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JDP2	NM_001135048.2	c.-23-4080A>G		intron_variant	Intron 1 of 3	ENST00000651602.1	NP_001128520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JDP2	ENST00000651602.1	c.-23-4080A>G		intron_variant	Intron 1 of 3		NM_001135048.2	ENSP00000498745.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59549 AN: 151628 Hom.: 13069 Cov.: 30

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.393 AC: 59568 AN: 151748 Hom.: 13079 Cov.: 30 AF XY: 0.394 AC XY: 29195 AN XY: 74124

African (AFR) AF: 0.182 AC: 7523 AN: 41356

American (AMR) AF: 0.383 AC: 5850 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2479 AN: 5144

South Asian (SAS) AF: 0.375 AC: 1800 AN: 4806

European-Finnish (FIN) AF: 0.514 AC: 5400 AN: 10506

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33763 AN: 67902

Other (OTH) AF: 0.409 AC: 864 AN: 2110

Alfa AF: 0.442 Hom.: 7700

Bravo AF: 0.379

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		-0.23
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: rs715463; hg19: chr14-75900521;