rs2299679

Variant names:

• chr20-9428939-C-A
• rs2299679
• NM_001377142.1:c.2524+4987C>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.2524+4987C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,044 control chromosomes in the GnomAD database, including 6,701 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 0.26 (6701 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 2 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, SD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377142.1. 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
	PLCB4	NM_001377142.1	MANE Select	c.2524+4987C>A		intron	N/A	NP_001364071.1	A0A7P0MRI8
	PLCB4	NM_001377143.1		c.2524+4987C>A		intron	N/A	NP_001364072.1	A0A7P0MRI8
	PLCB4	NM_000933.4		c.2488+4987C>A		intron	N/A	NP_000924.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.2524+4987C>A		intron	N/A	ENSP00000367734.5	A0A7P0MRI8
	PLCB4	ENST00000278655.9	TSL:1	c.2434+4987C>A		intron	N/A	ENSP00000278655.5	A0A8I5KRP3
	PLCB4	ENST00000464199.5	TSL:1	n.2265+4987C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39735 AN: 151926 Hom.: 6675 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.262 AC: 39814 AN: 152044 Hom.: 6701 Cov.: 32 AF XY: 0.257 AC XY: 19102 AN XY: 74328

African (AFR) AF: 0.470 AC: 19477 AN: 41424

American (AMR) AF: 0.241 AC: 3681 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1890 AN: 5154

South Asian (SAS) AF: 0.121 AC: 583 AN: 4816

European-Finnish (FIN) AF: 0.106 AC: 1118 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12004 AN: 68000

Other (OTH) AF: 0.221 AC: 467 AN: 2114

Alfa AF: 0.236 Hom.: 5386

Bravo AF: 0.284

Asia WGS AF: 0.236 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		0.88
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: rs2299679; hg19: chr20-9409586;