Genetic Variant PLEKHG1:c.*1083G>A (chr6-150841979-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001029884.3(PLEKHG1):c.*1083G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,010 control chromosomes in the GnomAD database, including 1,884 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 0.15 ( 1884 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

PLEKHG1
NM_001029884.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

13 publications found

Variant links:

Genes affected

PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG1 Gene-Disease associations (from GenCC):

periventricular leukomalacia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PLEKHG1 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029884.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHG1	NM_001029884.3	MANE Select	c.*1083G>A	3_prime_UTR	Exon 17 of 17	NP_001025055.1	Q9ULL1
PLEKHG1	NM_001329798.2		c.*1083G>A	3_prime_UTR	Exon 16 of 16	NP_001316727.1
PLEKHG1	NM_001329799.2		c.*1083G>A	3_prime_UTR	Exon 16 of 16	NP_001316728.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHG1	ENST00000696526.1	MANE Select	c.*1083G>A	3_prime_UTR	Exon 17 of 17	ENSP00000512689.1	Q9ULL1
PLEKHG1	ENST00000475490.1	TSL:1	n.*220G>A	non_coding_transcript_exon	Exon 15 of 15	ENSP00000433107.1	H0YD71
PLEKHG1	ENST00000475490.1	TSL:1	n.*220G>A	3_prime_UTR	Exon 15 of 15	ENSP00000433107.1	H0YD71

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22163

AN:

151892

Hom.:

1881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.148

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.146

AC:

22180

AN:

152010

Hom.:

1884

Cov.:

AF XY:

0.148

AC XY:

10965

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0483

AC:

2005

AN:

41494

American (AMR)

AF:

0.189

AC:

2887

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

501

AN:

3468

East Asian (EAS)

AF:

0.127

AC:

655

AN:

5172

South Asian (SAS)

AF:

0.199

AC:

956

AN:

4812

European-Finnish (FIN)

AF:

0.197

AC:

2072

AN:

10528

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12590

AN:

67958

Other (OTH)

AF:

0.153

AC:

323

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

969

1938

2908

3877

4846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.169

Hom.:

7876

Bravo

AF:

0.140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.21

(source)

DANN

Benign

0.44

PhyloP100

-1.6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over