NM_001377142.1:c.61G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377142.1(PLCB4):c.61G>A(p.Ala21Thr) variant causes a missense change. The variant allele was found at a frequency of 0.633 in 1,557,610 control chromosomes in the GnomAD database, including 323,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A21E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.52 ( 23573 hom., cov: 31)

Exomes 𝑓: 0.65 ( 299964 hom. )

Consequence

PLCB4
NM_001377142.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.01

Publications

43 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, AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0471891E-5).

BP6

Variant 20-9307875-G-A is Benign according to our data. Variant chr20-9307875-G-A is described in ClinVar as Benign. ClinVar VariationId is 339552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

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
PLCB4	NM_001377142.1	MANE Select	c.61G>A	p.Ala21Thr	missense	Exon 4 of 40	NP_001364071.1
PLCB4	NM_001377143.1		c.61G>A	p.Ala21Thr	missense	Exon 3 of 39	NP_001364072.1
PLCB4	NM_000933.4		c.61G>A	p.Ala21Thr	missense	Exon 4 of 39	NP_000924.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.61G>A	p.Ala21Thr	missense	Exon 4 of 40	ENSP00000367734.5
PLCB4	ENST00000278655.9	TSL:1	c.61G>A	p.Ala21Thr	missense	Exon 3 of 36	ENSP00000278655.5
PLCB4	ENST00000946820.1		c.61G>A	p.Ala21Thr	missense	Exon 4 of 40	ENSP00000616879.1

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78385

AN:

151814

Hom.:

23566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.673

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.565

GnomAD2 exomes

AF:

0.596

AC:

147393

AN:

247122

AF XY:

0.610

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.713

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.646

AC:

907575

AN:

1405678

Hom.:

299964

Cov.:

AF XY:

0.648

AC XY:

454891

AN XY:

702170

show subpopulations

African (AFR)

AF:

0.175

AC:

5745

AN:

32814

American (AMR)

AF:

0.589

AC:

26000

AN:

44110

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

18072

AN:

25686

East Asian (EAS)

AF:

0.442

AC:

17329

AN:

39184

South Asian (SAS)

AF:

0.623

AC:

52330

AN:

84010

European-Finnish (FIN)

AF:

0.534

AC:

28330

AN:

53040

Middle Eastern (MID)

AF:

0.664

AC:

3758

AN:

5662

European-Non Finnish (NFE)

AF:

0.677

AC:

719114

AN:

1062668

Other (OTH)

AF:

0.631

AC:

36897

AN:

58504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

12274

24548

36823

49097

61371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17940

35880

53820

71760

89700

<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:

0.516

AC:

78393

AN:

151932

Hom.:

23573

Cov.:

AF XY:

0.512

AC XY:

38046

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.192

AC:

7967

AN:

41430

American (AMR)

AF:

0.577

AC:

8810

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

2445

AN:

3472

East Asian (EAS)

AF:

0.454

AC:

2344

AN:

5162

South Asian (SAS)

AF:

0.622

AC:

2999

AN:

4818

European-Finnish (FIN)

AF:

0.534

AC:

5620

AN:

10524

Middle Eastern (MID)

AF:

0.666

AC:

193

AN:

290

European-Non Finnish (NFE)

AF:

0.679

AC:

46136

AN:

67960

Other (OTH)

AF:

0.570

AC:

1202

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1606

3212

4817

6423

8029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.647

Hom.:

84613

Bravo

AF:

0.505

TwinsUK

AF:

0.685

AC:

2539

ALSPAC

AF:

0.680

AC:

2621

ESP6500AA

AF:

0.211

AC:

930

ESP6500EA

AF:

0.673

AC:

5785

ExAC

AF:

0.593

AC:

72006

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Auriculocondylar syndrome 2 (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.000010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

6.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Benign

0.35

Sift4G

Benign

0.44

Polyphen

0.99

Vest4

0.30

MPC

0.69

ClinPred

0.018

GERP RS

5.9

Varity_R

0.20

gMVP

0.24

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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