rs2179321

Variant names:

• chr20-9391178-G-T
• rs2179321
• NM_001377142.1:c.1323+563G>T

Variant summary

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

The NM_001377142.1(PLCB4):​c.1323+563G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,062 control chromosomes in the GnomAD database, including 31,200 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 0.61 (31200 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	NM_001377142.1	MANE Select	c.1323+563G>T		intron	N/A	NP_001364071.1
	PLCB4	NM_001377143.1		c.1323+563G>T		intron	N/A	NP_001364072.1
	PLCB4	NM_000933.4		c.1323+563G>T		intron	N/A	NP_000924.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.1323+563G>T		intron	N/A	ENSP00000367734.5
	PLCB4	ENST00000278655.9	TSL:1	c.1269+563G>T		intron	N/A	ENSP00000278655.5
	PLCB4	ENST00000464199.5	TSL:1	n.1100+563G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93040 AN: 151944 Hom.: 31142 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.613 AC: 93148 AN: 152062 Hom.: 31200 Cov.: 32 AF XY: 0.607 AC XY: 45093 AN XY: 74306

African (AFR) AF: 0.908 AC: 37712 AN: 41524

American (AMR) AF: 0.535 AC: 8171 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3265 AN: 5164

South Asian (SAS) AF: 0.548 AC: 2634 AN: 4810

European-Finnish (FIN) AF: 0.411 AC: 4342 AN: 10554

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33542 AN: 67956

Other (OTH) AF: 0.581 AC: 1224 AN: 2108

Alfa AF: 0.538 Hom.: 69951

Bravo AF: 0.637

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		0.35
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: rs2179321; hg19: chr20-9371825;