dbSNP rs6056188: PLCB1:c.3423+40920A>G (chr20-8831181-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015192.4(PLCB1):c.3423+40920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,792 control chromosomes in the GnomAD database, including 19,917 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 0.50 ( 19831 hom., cov: 32)

Exomes 𝑓: 0.40 ( 86 hom. )

Consequence

PLCB1
NM_015192.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.493

Publications

1 publications found

Variant links:

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 1) 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. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PLCB1 links:

RNU105B (HGNC:10103): (RNA, U105B small nucleolar)

RNU105B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.3423+40920A>G	intron_variant	Intron 31 of 31	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 link	c.*19+29008A>G	intron_variant	Intron 32 of 32		NP_877398.1	Q9NQ66-2
RNU105B	NR_004386.2 link	n.-4A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 link	c.3423+40920A>G		intron_variant	Intron 31 of 31	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76533

AN:

151814

Hom.:

19821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.523

GnomAD4 exome

AF:

0.400

AC:

344

AN:

860

Hom.:

Cov.:

AF XY:

0.416

AC XY:

223

AN XY:

536

show subpopulations

African (AFR)

AF:

0.550

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.0750

AC:

AN:

South Asian (SAS)

AF:

0.429

AC:

AN:

European-Finnish (FIN)

AF:

0.429

AC:

AN:

154

Middle Eastern (MID)

AF:

0.618

AC:

AN:

European-Non Finnish (NFE)

AF:

0.409

AC:

203

AN:

496

Other (OTH)

AF:

0.479

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.504

AC:

76571

AN:

151932

Hom.:

19831

Cov.:

AF XY:

0.501

AC XY:

37171

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.594

AC:

24592

AN:

41432

American (AMR)

AF:

0.428

AC:

6533

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1882

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1172

AN:

5158

South Asian (SAS)

AF:

0.519

AC:

2495

AN:

4806

European-Finnish (FIN)

AF:

0.482

AC:

5073

AN:

10534

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33058

AN:

67946

Other (OTH)

AF:

0.524

AC:

1104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1874

3749

5623

7498

9372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.488

Hom.:

4494

Bravo

AF:

0.499

Asia WGS

AF:

0.385

AC:

1343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.5

(source)

DANN

Benign

0.61

PhyloP100

-0.49

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over