chr20-9244517-C-G

Variant names:

• chr20-9244517-C-G
• rs6039424
• NM_001377142.1:c.-16+27065C>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.-16+27065C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,684 control chromosomes in the GnomAD database, including 23,228 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 (23228 hom., cov: 31)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.-16+27065C>G		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.-16+27065C>G		intron_variant	Intron 3 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78654 AN: 151566 Hom.: 23175 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.519 AC: 78771 AN: 151684 Hom.: 23228 Cov.: 31 AF XY: 0.525 AC XY: 38903 AN XY: 74116

African (AFR) AF: 0.810 AC: 33583 AN: 41466

American (AMR) AF: 0.529 AC: 8059 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1278 AN: 3462

East Asian (EAS) AF: 0.695 AC: 3586 AN: 5158

South Asian (SAS) AF: 0.520 AC: 2497 AN: 4798

European-Finnish (FIN) AF: 0.403 AC: 4213 AN: 10454

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 23984 AN: 67804

Other (OTH) AF: 0.495 AC: 1041 AN: 2104

Alfa AF: 0.254 Hom.: 591

Bravo AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.21
PhyloP100		-0.26
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: rs6039424; hg19: chr20-9225164;