rs2142731

Positions:

• chr6-28283136-A-G

Variant summary

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

The NM_032507.4(PGBD1):​c.-38-640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,276 control chromosomes in the GnomAD database, including 247 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 0.033 (247 hom., cov: 32)
• Consequence: PGBD1 NM_032507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.84

Genes affected

PGBD1 (HGNC:19398): (piggyBac transposable element derived 1) The piggyBac family of proteins, found in diverse animals, are transposases related to the transposase of the canonical piggyBac transposon from the moth, Trichoplusia ni. This family also includes genes in several genomes, including human, that appear to have been derived from the piggyBac transposons. This gene belongs to the subfamily of piggyBac transposable element derived (PGBD) genes. The PGBD proteins appear to be novel, with no obvious relationship to other transposases, or other known protein families. This gene product is specifically expressed in the brain, however, its exact function is not known. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGBD1	NM_032507.4	c.-38-640A>G		intron_variant		ENST00000682144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGBD1	ENST00000682144.1	c.-38-640A>G		intron_variant			NM_032507.4	P1
PGBD1	ENST00000259883.3	c.-58-620A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5064 AN: 152158 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0333 AC: 5064 AN: 152276 Hom.: 247 Cov.: 32 AF XY: 0.0357 AC XY: 2658 AN XY: 74470

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.00388

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0124 Hom.: 75

Bravo AF: 0.0405

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.43

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: rs2142731; hg19: chr6-28250913;