rs6056625

Variant names:

• chr20-9439967-A-G
• rs6056625
• NM_001377142.1:c.2764+2815A>G

Variant summary

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

The NM_001377142.1(PLCB4):​c.2764+2815A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,178 control chromosomes in the GnomAD database, including 5,121 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 0.24 (5121 hom., cov: 33)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.2764+2815A>G		intron_variant	Intron 30 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.2764+2815A>G		intron_variant	Intron 30 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35942 AN: 152060 Hom.: 5104 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.237 AC: 35995 AN: 152178 Hom.: 5121 Cov.: 33 AF XY: 0.232 AC XY: 17294 AN XY: 74396

African (AFR) AF: 0.385 AC: 15988 AN: 41484

American (AMR) AF: 0.229 AC: 3509 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1900 AN: 5164

South Asian (SAS) AF: 0.0985 AC: 475 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1162 AN: 10612

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11988 AN: 68010

Other (OTH) AF: 0.199 AC: 419 AN: 2108

Alfa AF: 0.201 Hom.: 3945

Bravo AF: 0.256

Asia WGS AF: 0.222 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		0.022
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: rs6056625; hg19: chr20-9420614;