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GeneBe

20-41166245-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002660.3(PLCG1):c.1851G>A(p.Gly617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,144 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 7 hom., cov: 32)
Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

PLCG1
NM_002660.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.949
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-41166245-G-A is Benign according to our data. Variant chr20-41166245-G-A is described in ClinVar as [Benign]. Clinvar id is 789125.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.949 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1229 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLCG1NM_002660.3 linkuse as main transcriptc.1851G>A p.Gly617= synonymous_variant 17/32 ENST00000685551.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLCG1ENST00000685551.1 linkuse as main transcriptc.1851G>A p.Gly617= synonymous_variant 17/32 NM_002660.3 P3P19174-2
PLCG1ENST00000373271.5 linkuse as main transcriptc.1851G>A p.Gly617= synonymous_variant 17/321 A1P19174-1
PLCG1ENST00000244007.7 linkuse as main transcriptc.1851G>A p.Gly617= synonymous_variant 18/335 P3P19174-2
PLCG1ENST00000465571.2 linkuse as main transcriptn.72G>A non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00807
AC:
1229
AN:
152250
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00263
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.00896
Gnomad ASJ
AF:
0.0219
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00734
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0115
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00824
AC:
2071
AN:
251408
Hom.:
15
AF XY:
0.00840
AC XY:
1141
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00209
Gnomad AMR exome
AF:
0.00584
Gnomad ASJ exome
AF:
0.0200
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00284
Gnomad FIN exome
AF:
0.00712
Gnomad NFE exome
AF:
0.0117
Gnomad OTH exome
AF:
0.00961
GnomAD4 exome
AF:
0.0109
AC:
15881
AN:
1461776
Hom.:
106
Cov.:
34
AF XY:
0.0107
AC XY:
7767
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00209
Gnomad4 AMR exome
AF:
0.00691
Gnomad4 ASJ exome
AF:
0.0225
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00292
Gnomad4 FIN exome
AF:
0.00711
Gnomad4 NFE exome
AF:
0.0123
Gnomad4 OTH exome
AF:
0.0103
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00805
AC:
1227
AN:
152368
Hom.:
7
Cov.:
32
AF XY:
0.00758
AC XY:
565
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00262
Gnomad4 AMR
AF:
0.00895
Gnomad4 ASJ
AF:
0.0219
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.00734
Gnomad4 NFE
AF:
0.0115
Gnomad4 OTH
AF:
0.0113
Alfa
AF:
0.0102
Hom.:
3
Bravo
AF:
0.00841
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0100
EpiControl
AF:
0.0122

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
8.1
Dann
Benign
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35256607; hg19: chr20-39794885; API