20-41168825-T-C

Variant names:

Variant summary

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

The NM_002660.3(PLCG1):c.2438T>C(p.Ile813Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,610,688 control chromosomes in the GnomAD database, including 281,299 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 36168 hom., cov: 33)

Exomes 𝑓: 0.57 ( 245131 hom. )

Consequence

PLCG1
NM_002660.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

94 publications found

Variant links:

Genes affected

PLCG1 (HGNC:9065): (phospholipase C gamma 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 receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PLCG1 links:

MIR6871 (HGNC:49964): (microRNA 6871) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6871 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 (MetaRNN=1.4687835E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG1	NM_002660.3 link	c.2438T>C	p.Ile813Thr	missense_variant	Exon 21 of 32	ENST00000685551.1	NP_002651.2	P19174-2Q4LE43Q9UFY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG1	ENST00000685551.1 link	c.2438T>C	p.Ile813Thr	missense_variant	Exon 21 of 32		NM_002660.3	ENSP00000508698.1		P19174-2

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101786

AN:

151998

Hom.:

36106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.825

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.641

GnomAD2 exomes

AF:

0.611

AC:

153388

AN:

250944

AF XY:

0.602

show subpopulations

Gnomad AFR exome

AF:

0.926

Gnomad AMR exome

AF:

0.604

Gnomad ASJ exome

AF:

0.579

Gnomad EAS exome

AF:

0.813

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.574

AC:

837726

AN:

1458572

Hom.:

245131

Cov.:

AF XY:

0.574

AC XY:

416768

AN XY:

725772

show subpopulations

African (AFR)

AF:

0.933

AC:

31183

AN:

33430

American (AMR)

AF:

0.609

AC:

27216

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

15086

AN:

26104

East Asian (EAS)

AF:

0.831

AC:

32992

AN:

39682

South Asian (SAS)

AF:

0.599

AC:

51560

AN:

86140

European-Finnish (FIN)

AF:

0.584

AC:

31178

AN:

53386

Middle Eastern (MID)

AF:

0.607

AC:

3086

AN:

5088

European-Non Finnish (NFE)

AF:

0.549

AC:

609525

AN:

1109858

Other (OTH)

AF:

0.596

AC:

35900

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16195

32391

48586

64782

80977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.670

AC:

101913

AN:

152116

Hom.:

36168

Cov.:

AF XY:

0.669

AC XY:

49774

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.921

AC:

38244

AN:

41538

American (AMR)

AF:

0.619

AC:

9466

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

1963

AN:

3466

East Asian (EAS)

AF:

0.825

AC:

4252

AN:

5156

South Asian (SAS)

AF:

0.597

AC:

2879

AN:

4822

European-Finnish (FIN)

AF:

0.576

AC:

6093

AN:

10584

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.545

AC:

37047

AN:

67946

Other (OTH)

AF:

0.643

AC:

1355

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.587

Hom.:

124937

Bravo

AF:

0.684

TwinsUK

AF:

0.545

AC:

2022

ALSPAC

AF:

0.550

AC:

2120

ESP6500AA

AF:

0.918

AC:

4043

ESP6500EA

AF:

0.542

AC:

4662

ExAC

AF:

0.614

AC:

74563

Asia WGS

AF:

0.697

AC:

2423

AN:

3478

EpiCase

AF:

0.539

EpiControl

AF:

0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.27

.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.2

N;N

PhyloP100

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.21

Sift

Benign

0.55

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.057

ClinPred

0.0045

GERP RS

5.8

PromoterAI

0.016

Neutral

(source)

Varity_R

0.14

gMVP

0.27

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

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

20-41168825-T-C

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