rs4535211

Variant names:

• chr3-17031505-A-G
• rs4535211
• NM_001144382.2:c.3019-11369A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144382.2. 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
	PLCL2	NM_001144382.2	MANE Select	c.3019-11369A>G		intron	N/A	NP_001137854.1	Q9UPR0-1
	PLCL2	NM_015184.5		c.2641-11369A>G		intron	N/A	NP_055999.2	Q9UPR0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL2	ENST00000615277.5	TSL:1 MANE Select	c.3019-11369A>G		intron	N/A	ENSP00000478458.1	Q9UPR0-1
	PLCL2	ENST00000432376.5	TSL:1	c.2641-11369A>G		intron	N/A	ENSP00000412836.1	Q9UPR0-3
	PLCL2	ENST00000955152.1		c.2815-11369A>G		intron	N/A	ENSP00000625211.1

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

African (AFR) AF: 0.708 AC: 29397 AN: 41506

American (AMR) AF: 0.569 AC: 8679 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1793 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3297 AN: 5166

South Asian (SAS) AF: 0.651 AC: 3138 AN: 4820

European-Finnish (FIN) AF: 0.639 AC: 6773 AN: 10592

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35588 AN: 67968

Other (OTH) AF: 0.582 AC: 1230 AN: 2114

Alfa AF: 0.562 Hom.: 9852

Bravo AF: 0.597

Asia WGS AF: 0.674 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4535211; hg19: chr3-17072997;