rs12446319

Positions:

• chr16-81741193-T-C

Variant summary

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

The variant allele was found at a frequency of 0.421 in 151,934 control chromosomes in the GnomAD database, including 13,865 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 (13865 hom., cov: 31)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

(HGNC:):

ENSG00000289733 (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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.81741193T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000261218	ENST00000563954.6	n.414+1757T>C		intron_variant		3
ENSG00000289733	ENST00000565054.6	n.316+1808T>C		intron_variant		5		ENSP00000520638.1
ENSG00000261218	ENST00000565272.5	n.420+814T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63868 AN: 151816 Hom.: 13862 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.421 AC: 63902 AN: 151934 Hom.: 13865 Cov.: 31 AF XY: 0.430 AC XY: 31949 AN XY: 74250

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.413

Alfa AF: 0.419 Hom.: 19048

Bravo AF: 0.411

Asia WGS AF: 0.624 AC: 2169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.75
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12446319; hg19: chr16-81774798;