rs4535211

chr3-17031505-A-G

Variant summary

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

The NM_001144382.2(PLCL2):c.3019-11369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,098 control chromosomes in the GnomAD database, including 27,565 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 0.60 (27565 hom., cov: 32)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL2	NM_001144382.2	c.3019-11369A>G		intron_variant		ENST00000615277.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL2	ENST00000615277.5	c.3019-11369A>G		intron_variant		1	NM_001144382.2
PLCL2	ENST00000432376.5	c.2641-11369A>G		intron_variant		1		P1
PLCL2	ENST00000419842.1	c.1872-11369A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90627 AN: 151978 Hom.: 27520 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.597 AC: 90737 AN: 152098 Hom.: 27565 Cov.: 32 AF XY: 0.601 AC XY: 44660 AN XY: 74358

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.582

Alfa AF: 0.564 Hom.: 6549

Bravo AF: 0.597

Asia WGS AF: 0.674 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.77
Dann	Benign	0.36

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: rs4535211; hg19: chr3-17072997;