Variant rs2071812 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.1636+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00938 in 1,196,170 control chromosomes in the GnomAD database, including 291 homozygotes. There are 3,733 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., 418 hem., cov: 21)

Exomes 𝑓: 0.0091 ( 252 hom. 3315 hem. )

Consequence

FGD1
NM_004463.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.67

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:

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=-0.78).

BP6

Variant X-54465430-G-A is Benign according to our data. Variant chrX-54465430-G-A is described in ClinVar as [Benign]. Clinvar id is 259402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD1	NM_004463.3 linkuse as main transcript	c.1636+21C>T		intron_variant		ENST00000375135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD1	ENST00000375135.4 linkuse as main transcript	c.1636+21C>T		intron_variant		1	NM_004463.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1328

AN:

110050

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

418

AN XY:

32324

show subpopulations

Gnomad AFR

AF:

0.00382

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.000380

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.00378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.0228

GnomAD3 exomes

AF:

0.0265

AC:

4534

AN:

171389

Hom.:

168

AF XY:

0.0228

AC XY:

1326

AN XY:

58253

show subpopulations

Gnomad AFR exome

AF:

0.00354

Gnomad AMR exome

AF:

0.0829

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.0283

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.00911

AC:

9893

AN:

1086067

Hom.:

252

Cov.:

AF XY:

0.00935

AC XY:

3315

AN XY:

354671

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.0834

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.00345

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0121

AC:

1330

AN:

110103

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

418

AN XY:

32387

show subpopulations

Gnomad4 AFR

AF:

0.00381

Gnomad4 AMR

AF:

0.0634

Gnomad4 ASJ

AF:

0.000380

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0215

Gnomad4 FIN

AF:

0.00378

Gnomad4 NFE

AF:

0.00167

Gnomad4 OTH

AF:

0.0225

Alfa

AF:

0.00577

Hom.:

Bravo

AF:

0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.1

DANN

Benign

0.67

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