rs8045964

Positions:

• chr16-81783128-C-T

Variant summary

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

The NM_002661.5(PLCG2):​c.-47-2815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 489,572 control chromosomes in the GnomAD database, including 50,431 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 0.42 (13640 hom., cov: 30)
  • Exomes 𝑓: 0.46 (36791 hom.)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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 (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.-47-2815C>T		intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.-47-2815C>T		intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63791 AN: 151652 Hom.: 13632 Cov.: 30

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.389

GnomAD3 exomes AF: 0.428 AC: 78888 AN: 184232 Hom.: 17634 AF XY: 0.442 AC XY: 44693 AN XY: 101136

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.631

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.400

GnomAD4 exome AF: 0.456 AC: 154110 AN: 337802 Hom.: 36791 Cov.: 0 AF XY: 0.472 AC XY: 91091 AN XY: 192886

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.633

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.421 AC: 63833 AN: 151770 Hom.: 13640 Cov.: 30 AF XY: 0.425 AC XY: 31545 AN XY: 74150

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.390

Alfa AF: 0.419 Hom.: 4006

Bravo AF: 0.404

Asia WGS AF: 0.429 AC: 1491 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	1.5
DANN	Benign	0.55

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: rs8045964; hg19: chr16-81816733; COSMIC: COSV63869127; COSMIC: COSV63869127;