Variant chr20-9362753-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001377142.1(PLCB4):c.370-143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 628,034 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 106 hom., cov: 33)

Exomes 𝑓: 0.035 ( 429 hom. )

Consequence

PLCB4
NM_001377142.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.615

Variant links:

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 links:

PLCB4 (HGNC:):

PLCB4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 20-9362753-A-G is Benign according to our data. Variant chr20-9362753-A-G is described in ClinVar as [Benign]. Clinvar id is 1275561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0295 (4495/152324) while in subpopulation NFE AF= 0.0471 (3201/68024). AF 95% confidence interval is 0.0457. There are 106 homozygotes in gnomad4. There are 2156 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 106 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1 linkuse as main transcript	c.370-143A>G		intron_variant		ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9 linkuse as main transcript	c.370-143A>G		intron_variant		1	NM_001377142.1	ENSP00000367734.5		A0A7P0MRI8

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4496

AN:

152206

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00741

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0478

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0471

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0353

AC:

16773

AN:

475710

Hom.:

429

AF XY:

0.0340

AC XY:

8655

AN XY:

254218

show subpopulations

Gnomad4 AFR exome

AF:

0.00826

Gnomad4 AMR exome

AF:

0.0166

Gnomad4 ASJ exome

AF:

0.00761

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.0453

Gnomad4 NFE exome

AF:

0.0470

Gnomad4 OTH exome

AF:

0.0301

GnomAD4 genome

AF:

0.0295

AC:

4495

AN:

152324

Hom.:

106

Cov.:

AF XY:

0.0289

AC XY:

2156

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00738

Gnomad4 AMR

AF:

0.0230

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0478

Gnomad4 NFE

AF:

0.0471

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0437

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

DANN

Benign

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over