NM_004573.3:c.3210-216C>A

Variant names:

• chr15-40290298-G-T
• rs936211
• NM_004573.3:c.3210-216C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004573.3(PLCB2):​c.3210-216C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,986 control chromosomes in the GnomAD database, including 6,319 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 0.27 (6319 hom., cov: 32)
• Consequence: PLCB2 NM_004573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 5 publications found

Genes affected

PLCB2 (HGNC:9055): (phospholipase C beta 2) The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB2	NM_004573.3	c.3210-216C>A		intron_variant	Intron 29 of 31	ENST00000260402.8	NP_004564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB2	ENST00000260402.8	c.3210-216C>A		intron_variant	Intron 29 of 31	2	NM_004573.3	ENSP00000260402.3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41453 AN: 151868 Hom.: 6316 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.273 AC: 41478 AN: 151986 Hom.: 6319 Cov.: 32 AF XY: 0.276 AC XY: 20507 AN XY: 74284

African (AFR) AF: 0.324 AC: 13397 AN: 41410

American (AMR) AF: 0.231 AC: 3523 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3472

East Asian (EAS) AF: 0.658 AC: 3378 AN: 5136

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4816

European-Finnish (FIN) AF: 0.312 AC: 3301 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15339 AN: 67968

Other (OTH) AF: 0.254 AC: 534 AN: 2104

Alfa AF: 0.227 Hom.: 1563

Bravo AF: 0.273

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.75
PhyloP100		-0.32
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs936211; hg19: chr15-40582499;