Genetic Variant PLCB4:p.Leu154Leu (chr20-9365473-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.38

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

auriculocondylar syndrome 2
Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
auriculocondylar syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PLCB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

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 Benign/Likely_benign. ClinVar VariationId is 339554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000257 (373/1453962) while in subpopulation MID AF = 0.00191 (11/5746). AF 95% confidence interval is 0.00107. There are 0 homozygotes in GnomAdExome4. There are 218 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377142.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCB4	NM_001377142.1	MANE Select	c.462G>A	p.Leu154Leu	synonymous	Exon 9 of 40	NP_001364071.1	A0A7P0MRI8
PLCB4	NM_001377143.1		c.462G>A	p.Leu154Leu	synonymous	Exon 8 of 39	NP_001364072.1	A0A7P0MRI8
PLCB4	NM_000933.4		c.462G>A	p.Leu154Leu	synonymous	Exon 9 of 39	NP_000924.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.462G>A	p.Leu154Leu	synonymous	Exon 9 of 40	ENSP00000367734.5	A0A7P0MRI8
PLCB4	ENST00000278655.9	TSL:1	c.449+2498G>A		intron	N/A	ENSP00000278655.5	A0A8I5KRP3
PLCB4	ENST00000946820.1		c.462G>A	p.Leu154Leu	synonymous	Exon 9 of 40	ENSP00000616879.1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000507

AC:

127

AN:

250516

AF XY:

0.000591

show subpopulations

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 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.:

Cov.:

AF XY:

0.000301

AC XY:

218

AN XY:

723866

show subpopulations

African (AFR)

AF:

0.000391

AC:

AN:

33288

American (AMR)

AF:

0.000696

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

143

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000117

AC:

129

AN:

1105232

Other (OTH)

AF:

0.000732

AC:

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000315

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41548

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68040

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.000363

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Auriculocondylar syndrome 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

4.4

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over