Variant 12-32502151-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370298.3(FGD4):c.167-61986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 985,422 control chromosomes in the GnomAD database, including 2,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 273 hom., cov: 33)

Exomes 𝑓: 0.074 ( 2392 hom. )

Consequence

FGD4
NM_001370298.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0700

Variant links:

Genes affected

FGD4 (HGNC:19125): (FYVE, RhoGEF and PH domain containing 4) This gene encodes a protein that is involved in the regulation of the actin cytoskeleton and cell shape. This protein contains an actin filament-binding domain, which together with its Dbl homology domain and one of its pleckstrin homology domains, can form microspikes. This protein can activate MAPK8 independently of the actin filament-binding domain, and it is also involved in the activation of CDC42 via the exchange of bound GDP for free GTP. The activation of CDC42 also enables this protein to play a role in mediating the cellular invasion of Cryptosporidium parvum, an intracellular parasite that infects the gastrointestinal tract. Mutations in this gene can cause Charcot-Marie-Tooth disease type 4H (CMT4H), a disorder of the peripheral nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

FGD4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-32502151-C-T is Benign according to our data. Variant chr12-32502151-C-T is described in ClinVar as [Benign]. Clinvar id is 308277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD4	NM_001370298.3 linkuse as main transcript	c.167-61986C>T		intron_variant		ENST00000534526.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD4	ENST00000534526.7 linkuse as main transcript	c.167-61986C>T		intron_variant		5	NM_001370298.3

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7729

AN:

152132

Hom.:

273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0518

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.0988

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0738

Gnomad OTH

AF:

0.0556

GnomAD4 exome

AF:

0.0744

AC:

62017

AN:

833172

Hom.:

2392

Cov.:

AF XY:

0.0751

AC XY:

28896

AN XY:

384764

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0537

Gnomad4 EAS exome

AF:

0.00386

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0757

Gnomad4 OTH exome

AF:

0.0717

GnomAD4 genome

AF:

0.0507

AC:

7726

AN:

152250

Hom.:

273

Cov.:

AF XY:

0.0490

AC XY:

3649

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.0508

Gnomad4 ASJ

AF:

0.0518

Gnomad4 EAS

AF:

0.00462

Gnomad4 SAS

AF:

0.0990

Gnomad4 FIN

AF:

0.0350

Gnomad4 NFE

AF:

0.0738

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0727

Hom.:

459

Bravo

AF:

0.0506

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2020	- -

Charcot-Marie-Tooth disease type 4H

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

-0.59

CADD

Benign

DANN

Benign

0.90

Splicing

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