16-81780739-T-C

Position:

• chr16-81780739-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.-48+1315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,202 control chromosomes in the GnomAD database, including 54,524 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 0.85 (54524 hom., cov: 32)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.96

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5	c.-48+1315T>C		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6	c.-48+1315T>C		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128636 AN: 152084 Hom.: 54478 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.846 AC: 128739 AN: 152202 Hom.: 54524 Cov.: 32 AF XY: 0.850 AC XY: 63254 AN XY: 74426

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.835

Alfa AF: 0.840 Hom.: 22677

Bravo AF: 0.842

Asia WGS AF: 0.926 AC: 3219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.35

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: rs4398100; hg19: chr16-81814344;