chr15-40303426-G-A

Variant names:

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

Variant summary

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

The NM_004573.3(PLCB2):​c.163-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,113,060 control chromosomes in the GnomAD database, including 232,056 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 0.60 (27953 hom., cov: 30)
  • Exomes 𝑓: 0.65 (204103 hom.)
• Consequence: PLCB2 NM_004573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 30 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB2	NM_004573.3	c.163-70C>T		intron_variant	Intron 2 of 31	ENST00000260402.8	NP_004564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB2	ENST00000260402.8	c.163-70C>T		intron_variant	Intron 2 of 31	2	NM_004573.3	ENSP00000260402.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91318 AN: 151698 Hom.: 27925 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.650 AC: 625050 AN: 961244 Hom.: 204103 AF XY: 0.649 AC XY: 323725 AN XY: 499020

African (AFR) AF: 0.540 AC: 12959 AN: 24000

American (AMR) AF: 0.770 AC: 32681 AN: 42450

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 14472 AN: 22656

East Asian (EAS) AF: 0.841 AC: 31510 AN: 37462

South Asian (SAS) AF: 0.681 AC: 51458 AN: 75582

European-Finnish (FIN) AF: 0.677 AC: 34907 AN: 51562

Middle Eastern (MID) AF: 0.662 AC: 3204 AN: 4838

European-Non Finnish (NFE) AF: 0.631 AC: 415824 AN: 658742

Other (OTH) AF: 0.638 AC: 28035 AN: 43952

GnomAD4 genome AF: 0.602 AC: 91397 AN: 151816 Hom.: 27953 Cov.: 30 AF XY: 0.610 AC XY: 45257 AN XY: 74182

African (AFR) AF: 0.529 AC: 21862 AN: 41356

American (AMR) AF: 0.676 AC: 10328 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2194 AN: 3464

East Asian (EAS) AF: 0.799 AC: 4116 AN: 5152

South Asian (SAS) AF: 0.673 AC: 3234 AN: 4802

European-Finnish (FIN) AF: 0.667 AC: 7057 AN: 10574

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40700 AN: 67880

Other (OTH) AF: 0.598 AC: 1260 AN: 2106

Alfa AF: 0.603 Hom.: 130298

Bravo AF: 0.600

Asia WGS AF: 0.724 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		0.18
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: rs1869901; hg19: chr15-40595627;