Variant chr1-6467536-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020631.6(PLEKHG5):c.*27T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,612,012 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 95 hom. )

Consequence

PLEKHG5
NM_020631.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.897

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-6467536-A-G is Benign according to our data. Variant chr1-6467536-A-G is described in ClinVar as [Benign]. Clinvar id is 297932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00642 (978/152252) while in subpopulation EAS AF= 0.0186 (96/5172). AF 95% confidence interval is 0.0156. There are 12 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG5	NM_020631.6 linkuse as main transcript	c.*27T>C		3_prime_UTR_variant	21/21	ENST00000377728.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG5	ENST00000377728.8 linkuse as main transcript	c.*27T>C		3_prime_UTR_variant	21/21	2	NM_020631.6	P2	O94827-5

Frequencies

GnomAD3 genomes

AF:

0.00644

AC:

979

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0110

AC:

2729

AN:

248780

Hom.:

AF XY:

0.0115

AC XY:

1544

AN XY:

134690

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.0161

Gnomad SAS exome

AF:

0.0204

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00655

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00692

AC:

10096

AN:

1459760

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

5420

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.0265

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.00454

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00642

AC:

978

AN:

152252

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0186

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00678

Hom.:

Bravo

AF:

0.00614

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, autosomal recessive 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.8

DANN

Benign

0.78

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