rs2299676

Variant names:

• chr20-9376790-G-A
• rs2299676
• NM_001377142.1:c.745-3264G>A

Variant summary

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

The NM_001377142.1(PLCB4):​c.745-3264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,984 control chromosomes in the GnomAD database, including 8,700 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 0.28 (8700 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 4 publications found

Genes affected

PLCB4 (HGNC:9059): (phospholipase C beta 4) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals in the retina. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2010]

PLCB4 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 2

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.745-3264G>A		intron_variant	Intron 12 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.745-3264G>A		intron_variant	Intron 12 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42214 AN: 151868 Hom.: 8667 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.278 AC: 42304 AN: 151984 Hom.: 8700 Cov.: 32 AF XY: 0.275 AC XY: 20439 AN XY: 74276

African (AFR) AF: 0.586 AC: 24272 AN: 41422

American (AMR) AF: 0.225 AC: 3441 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1243 AN: 5152

South Asian (SAS) AF: 0.141 AC: 676 AN: 4810

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9943 AN: 67972

Other (OTH) AF: 0.244 AC: 512 AN: 2096

Alfa AF: 0.187 Hom.: 9726

Bravo AF: 0.303

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.31
PhyloP100		-0.077
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: rs2299676; hg19: chr20-9357437;