chr15-40303426-G-C

Variant names:

• chr15-40303426-G-C
• rs1869901
• NM_004573.3:c.163-70C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004573.3(PLCB2):​c.163-70C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCB2 NM_004573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004573.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB2	NM_004573.3	MANE Select	c.163-70C>G		intron	N/A	NP_004564.2	Q00722-1
	PLCB2	NM_001284297.2		c.163-70C>G		intron	N/A	NP_001271226.1	Q00722-2
	PLCB2	NM_001284298.2		c.163-70C>G		intron	N/A	NP_001271227.1	Q00722-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB2	ENST00000260402.8	TSL:2 MANE Select	c.163-70C>G		intron	N/A	ENSP00000260402.3	Q00722-1
	PLCB2	ENST00000557821.5	TSL:1	c.163-70C>G		intron	N/A	ENSP00000453975.1	Q00722-2
	PLCB2	ENST00000456256.6	TSL:1	c.163-70C>G		intron	N/A	ENSP00000411991.2	Q00722-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 962260 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 499486

African (AFR) AF: 0.00 AC: 0 AN: 24026

American (AMR) AF: 0.00 AC: 0 AN: 42476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22670

East Asian (EAS) AF: 0.00 AC: 0 AN: 37464

South Asian (SAS) AF: 0.00 AC: 0 AN: 75636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 659544

Other (OTH) AF: 0.00 AC: 0 AN: 43990

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		0.18

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: rs1869901; hg19: chr15-40595627;