chr20-9272941-T-C

Variant names:

• chr20-9272941-T-C
• rs4816129
• NM_001377142.1:c.-15-34859T>C

Variant summary

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

The NM_001377142.1(PLCB4):​c.-15-34859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 150,800 control chromosomes in the GnomAD database, including 23,748 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 0.52 (23748 hom., cov: 28)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.72
• 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, 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.-15-34859T>C		intron_variant	Intron 3 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.-15-34859T>C		intron_variant	Intron 3 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 78691 AN: 150690 Hom.: 23694 Cov.: 28

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.523 AC: 78802 AN: 150800 Hom.: 23748 Cov.: 28 AF XY: 0.528 AC XY: 38860 AN XY: 73598

African (AFR) AF: 0.835 AC: 34213 AN: 40990

American (AMR) AF: 0.529 AC: 8009 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3464

East Asian (EAS) AF: 0.689 AC: 3480 AN: 5050

South Asian (SAS) AF: 0.516 AC: 2448 AN: 4742

European-Finnish (FIN) AF: 0.394 AC: 4082 AN: 10360

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23723 AN: 67764

Other (OTH) AF: 0.499 AC: 1048 AN: 2100

Alfa AF: 0.428 Hom.: 4034

Bravo AF: 0.549

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.44
PhyloP100		-5.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4816129; hg19: chr20-9253588;