NM_001144382.2:c.327+44080A>G

Variant names:

• chr3-16929446-A-G
• rs9821630
• NM_001144382.2:c.327+44080A>G

Variant summary

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

The NM_001144382.2(PLCL2):​c.327+44080A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,096 control chromosomes in the GnomAD database, including 5,342 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 0.24 (5342 hom., cov: 31)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

Genes affected

PLCL2 (HGNC:9064): (phospholipase C like 2) Enables GABA receptor binding activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including B cell activation; gamma-aminobutyric acid signaling pathway; and negative regulation of B cell receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL2	NM_001144382.2	c.327+44080A>G		intron_variant	Intron 1 of 5	ENST00000615277.5	NP_001137854.1
PLCL2	XM_047447799.1	c.-7418A>G		5_prime_UTR_variant	Exon 1 of 7		XP_047303755.1
PLCL2	XM_006713073.4	c.12+29762A>G		intron_variant	Intron 1 of 5		XP_006713136.1
PLCL2	XM_017006025.2	c.-155-8109A>G		intron_variant	Intron 1 of 6		XP_016861514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5	c.327+44080A>G		intron_variant	Intron 1 of 5	1	NM_001144382.2	ENSP00000478458.1
PLCL2	ENST00000460467.1	n.439-80228A>G		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36644 AN: 151978 Hom.: 5343 Cov.: 31

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.241 AC: 36648 AN: 152096 Hom.: 5342 Cov.: 31 AF XY: 0.248 AC XY: 18434 AN XY: 74332

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.247

Alfa AF: 0.261 Hom.: 2731

Bravo AF: 0.224

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9821630; hg19: chr3-16970938;