rs2224361

Positions:

• chr20-9244143-G-A
• chr20-9244143-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377142.1(PLCB4):​c.-16+26691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,192 control chromosomes in the GnomAD database, including 71,735 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 0.97 (71735 hom., cov: 30)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.-16+26691G>A		intron_variant		ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.-16+26691G>A		intron_variant		1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147601 AN: 152074 Hom.: 71672 Cov.: 30

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.981

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

GnomAD4 genome AF: 0.971 AC: 147724 AN: 152192 Hom.: 71735 Cov.: 30 AF XY: 0.971 AC XY: 72274 AN XY: 74408

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.958

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.982

Alfa AF: 0.956 Hom.: 32263

Bravo AF: 0.975

Asia WGS AF: 0.989 AC: 3439 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.010
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2224361; hg19: chr20-9224790;