chr2-28482090-G-A

Position:

• chr2-28482090-G-A

Variant summary

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

The ENST00000416713.5(PLB1):​c.-114+24893G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,160 control chromosomes in the GnomAD database, including 48,523 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 0.80 (48523 hom., cov: 33)
• Consequence: PLB1 ENST00000416713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLB1	ENST00000416713.5	c.-114+24893G>A		intron_variant		5		ENSP00000407076

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121328 AN: 152044 Hom.: 48507 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.798 AC: 121381 AN: 152160 Hom.: 48523 Cov.: 33 AF XY: 0.798 AC XY: 59350 AN XY: 74394

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.807

Alfa AF: 0.798 Hom.: 23825

Bravo AF: 0.795

Asia WGS AF: 0.809 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2338014; hg19: chr2-28704957;