ENST00000416713.5:c.-114+24893G>A

Variant names:

• chr2-28482090-G-A
• rs2338014
• ENST00000416713.5:c.-114+24893G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLB1	ENST00000416713.5	c.-114+24893G>A		intron_variant	Intron 1 of 10	5		ENSP00000407076.1

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

African (AFR) AF: 0.773 AC: 32055 AN: 41488

American (AMR) AF: 0.789 AC: 12072 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3182 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4575 AN: 5180

South Asian (SAS) AF: 0.736 AC: 3544 AN: 4814

European-Finnish (FIN) AF: 0.827 AC: 8753 AN: 10588

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.800 AC: 54429 AN: 68006

Other (OTH) AF: 0.807 AC: 1705 AN: 2114

Alfa AF: 0.800 Hom.: 36015

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
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs2338014; hg19: chr2-28704957;