2-28576908-A-G

Variant names:

• chr2-28576908-A-G
• rs2338545
• NM_153021.5:c.1434-1199A>G

Variant summary

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

The NM_153021.5(PLB1):​c.1434-1199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,052 control chromosomes in the GnomAD database, including 12,303 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 0.37 (12303 hom., cov: 32)
• Consequence: PLB1 NM_153021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153021.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLB1	NM_153021.5	MANE Select	c.1434-1199A>G		intron	N/A	NP_694566.4
	PLB1	NM_001170585.2		c.1467-1199A>G		intron	N/A	NP_001164056.1	Q6P1J6-3
	PLB1	NR_138141.2		n.593-1199A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLB1	ENST00000327757.10	TSL:1 MANE Select	c.1434-1199A>G		intron	N/A	ENSP00000330442.5	Q6P1J6-1
	PLB1	ENST00000422425.6	TSL:1	c.1467-1199A>G		intron	N/A	ENSP00000416440.2	Q6P1J6-3
	PLB1	ENST00000404858.5	TSL:1	c.1461-1199A>G		intron	N/A	ENSP00000384187.1	H7BYX7

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55830 AN: 151934 Hom.: 12276 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.368 AC: 55901 AN: 152052 Hom.: 12303 Cov.: 32 AF XY: 0.370 AC XY: 27508 AN XY: 74334

African (AFR) AF: 0.591 AC: 24489 AN: 41454

American (AMR) AF: 0.498 AC: 7609 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.407 AC: 2103 AN: 5162

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4814

European-Finnish (FIN) AF: 0.249 AC: 2640 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15944 AN: 67958

Other (OTH) AF: 0.343 AC: 724 AN: 2112

Alfa AF: 0.273 Hom.: 13057

Bravo AF: 0.402

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2338545; hg19: chr2-28799775;