20-9365473-G-A

Position:

• chr20-9365473-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2 BP4_Moderate BP6_Very_Strong BS1

The NM_001377142.1(PLCB4):​c.462G>A​(p.Leu154Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000262 in 1,606,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: PLCB4 NM_001377142.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 20-9365473-G-A is Benign according to our data. Variant chr20-9365473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 339554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000315 (48/152280) while in subpopulation AFR AF= 0.000289 (12/41548). AF 95% confidence interval is 0.000166. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.462G>A	p.Leu154Leu	synonymous_variant	9/40	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.462G>A	p.Leu154Leu	synonymous_variant	9/40	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000507 AC: 127 AN: 250516 Hom.: 0 AF XY: 0.000591 AC XY: 80 AN XY: 135436

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000671

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000257 AC: 373 AN: 1453962 Hom.: 0 Cov.: 27 AF XY: 0.000301 AC XY: 218 AN XY: 723866

Gnomad4 AFR exome AF: 0.000391

Gnomad4 AMR exome AF: 0.000696

Gnomad4 ASJ exome AF: 0.00548

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.000732

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74448

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000724 Hom.: 0

Bravo AF: 0.000363

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Auriculocondylar syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs142392531; hg19: chr20-9346120;