rs4888197

Positions:

• chr16-81950832-A-G
• chr16-81950832-A-T

Variant summary

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

The ENST00000564138.6(PLCG2):​c.3570+4569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,250 control chromosomes in the GnomAD database, including 1,411 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 0.13 (1411 hom., cov: 33)
• Consequence: PLCG2 ENST00000564138.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

Genes affected

PLCG2 (HGNC:9066): (phospholipase C gamma 2) The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.3570+4569A>G		intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.3570+4569A>G		intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20227 AN: 152132 Hom.: 1404 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.133 AC: 20268 AN: 152250 Hom.: 1411 Cov.: 33 AF XY: 0.130 AC XY: 9703 AN XY: 74442

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0979

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.153

Alfa AF: 0.131 Hom.: 1725

Bravo AF: 0.142

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.78

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: rs4888197; hg19: chr16-81984437;