rs2072910

Variant names:

• chr20-9384656-T-C
• rs2072910
• NM_001377142.1:c.1064+245T>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.1064+245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,038 control chromosomes in the GnomAD database, including 7,573 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 0.23 (7573 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 18 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.1064+245T>C		intron_variant	Intron 14 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.1064+245T>C		intron_variant	Intron 14 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34402 AN: 151922 Hom.: 7536 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.227 AC: 34497 AN: 152038 Hom.: 7573 Cov.: 32 AF XY: 0.226 AC XY: 16792 AN XY: 74310

African (AFR) AF: 0.575 AC: 23816 AN: 41414

American (AMR) AF: 0.185 AC: 2824 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5170

South Asian (SAS) AF: 0.0905 AC: 436 AN: 4818

European-Finnish (FIN) AF: 0.0624 AC: 659 AN: 10568

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0672 AC: 4566 AN: 67996

Other (OTH) AF: 0.200 AC: 420 AN: 2102

Alfa AF: 0.116 Hom.: 5034

Bravo AF: 0.256

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.56
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: rs2072910; hg19: chr20-9365303;