20-9337993-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001377142.1(PLCB4):​c.166-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,605,732 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 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PLCB4
NM_001377142.1 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 20-9337993-A-G is Benign according to our data. Variant chr20-9337993-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3698171.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000854 (13/152268) while in subpopulation AMR AF= 0.000785 (12/15280). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCB4NM_001377142.1 linkc.166-15A>G intron_variant Intron 5 of 39 ENST00000378473.9 NP_001364071.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCB4ENST00000378473.9 linkc.166-15A>G intron_variant Intron 5 of 39 1 NM_001377142.1 ENSP00000367734.5 A0A7P0MRI8

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000786
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250474
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135362
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.0000124
AC:
18
AN:
1453464
Hom.:
0
Cov.:
27
AF XY:
0.00000967
AC XY:
7
AN XY:
723740
show subpopulations
Gnomad4 AFR exome
AF:
0.0000601
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.0000833
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152268
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.000193

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.092
DANN
Benign
0.67

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.

Other links and lift over

dbSNP: rs533870825; hg19: chr20-9318640; API