rs4997772

Positions:

• chr16-81871690-T-C

Variant summary

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

The NM_002661.5(PLCG2):​c.648+755T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,990 control chromosomes in the GnomAD database, including 23,497 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 0.55 (23497 hom., cov: 32)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.648+755T>C		intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.648+755T>C		intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83070 AN: 151870 Hom.: 23472 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.547 AC: 83145 AN: 151990 Hom.: 23497 Cov.: 32 AF XY: 0.551 AC XY: 40887 AN XY: 74260

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.562

Alfa AF: 0.607 Hom.: 11616

Bravo AF: 0.537

Asia WGS AF: 0.602 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.64

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: rs4997772; hg19: chr16-81905295;