Variant X-54470556-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_StrongBA1

The NM_004463.3(FGD1):c.659+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,195,390 control chromosomes in the GnomAD database, including 7,374 homozygotes. There are 39,471 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 766 hom., 3916 hem., cov: 22)

Exomes 𝑓: 0.10 ( 6608 hom. 35555 hem. )

Consequence

FGD1
NM_004463.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

FGD1 (HGNC:3663): (FYVE, RhoGEF and PH domain containing 1) This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of the faciogenital dysplasia in Aarskog-Scott syndrome and a syndromatic form of X-linked cognitive disability. [provided by RefSeq, Jul 2017]

FGD1 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=-0.77).

BP6

Variant X-54470556-A-G is Benign according to our data. Variant chrX-54470556-A-G is described in ClinVar as [Benign]. Clinvar id is 259404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD1	NM_004463.3 linkuse as main transcript	c.659+27T>C		intron_variant		ENST00000375135.4	NP_004454.2	P98174A0A024R9Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGD1	ENST00000375135.4 linkuse as main transcript	c.659+27T>C		intron_variant		1	NM_004463.3	ENSP00000364277.3		P98174

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

12729

AN:

110921

Hom.:

768

Cov.:

AF XY:

0.118

AC XY:

3910

AN XY:

33181

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.0661

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0880

Gnomad MID

AF:

0.0429

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.156

AC:

26120

AN:

167371

Hom.:

2558

AF XY:

0.144

AC XY:

7858

AN XY:

54553

show subpopulations

Gnomad AFR exome

AF:

0.0997

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.0710

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0909

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.101

AC:

109449

AN:

1084415

Hom.:

6608

Cov.:

AF XY:

0.101

AC XY:

35555

AN XY:

351603

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.0694

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0898

Gnomad4 NFE exome

AF:

0.0749

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.115

AC:

12724

AN:

110975

Hom.:

766

Cov.:

AF XY:

0.118

AC XY:

3916

AN XY:

33245

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.0661

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.0880

Gnomad4 NFE

AF:

0.0755

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0912

Hom.:

5685

Bravo

AF:

0.132

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	May 11, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Aarskog syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.75

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