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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLCB1	NM_015192.4	MANE Select	c.3423+40920A>G	intron	N/A	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3		c.*19+29008A>G	intron	N/A	NP_877398.1	Q9NQ66-2
RNU105B	NR_004386.2		n.-4A>G	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLCB1	ENST00000338037.11	TSL:1 MANE Select	c.3423+40920A>G	intron	N/A	ENSP00000338185.6	Q9NQ66-1
PLCB1	ENST00000378641.7	TSL:1	c.*19+29008A>G	intron	N/A	ENSP00000367908.3	Q9NQ66-2
PLCB1	ENST00000487210.5	TSL:1	n.*19+29008A>G	intron	N/A	ENSP00000431704.1	H0YCJ2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over