dbSNP rs3007421: PLEKHG5:c.1800+107C>T (chr1-6470129-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020631.6(PLEKHG5):c.1800+107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,258,266 control chromosomes in the GnomAD database, including 13,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2974 hom., cov: 33)

Exomes 𝑓: 0.13 ( 10059 hom. )

Consequence

PLEKHG5
NM_020631.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.956

Variant links:

Genes affected

PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

PLEKHG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-6470129-G-A is Benign according to our data. Variant chr1-6470129-G-A is described in ClinVar as [Benign]. Clinvar id is 667938.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-6470129-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG5	NM_020631.6 link	c.1800+107C>T		intron_variant	Intron 16 of 20	ENST00000377728.8	NP_065682.2	O94827-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG5	ENST00000377728.8 link	c.1800+107C>T		intron_variant	Intron 16 of 20	2	NM_020631.6	ENSP00000366957.3		O94827-5

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26812

AN:

152064

Hom.:

2961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.126

AC:

139643

AN:

1106084

Hom.:

10059

AF XY:

0.127

AC XY:

70912

AN XY:

557104

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.0826

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.00784

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.177

AC:

26867

AN:

152182

Hom.:

2974

Cov.:

AF XY:

0.175

AC XY:

13029

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00483

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.130

Hom.:

837

Bravo

AF:

0.183

Asia WGS

AF:

0.116

AC:

403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.1

DANN

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over