12-32563911-G-A

Position:

• chr12-32563911-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001370298.3(FGD4):​c.167-226G>A variant causes a intron change. The variant allele was found at a frequency of 0.094 in 151,778 control chromosomes in the GnomAD database, including 1,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.094 (1049 hom., cov: 29)
• Consequence: FGD4 NM_001370298.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: No conservation score assigned

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-32563911-G-A is Benign according to our data. Variant chr12-32563911-G-A is described in ClinVar as [Benign]. Clinvar id is 1293247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD4	NM_001370298.3	c.167-226G>A		intron_variant		ENST00000534526.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD4	ENST00000534526.7	c.167-226G>A		intron_variant		5	NM_001370298.3

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14232 AN: 151658 Hom.: 1043 Cov.: 29

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0888

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0940 AC: 14261 AN: 151778 Hom.: 1049 Cov.: 29 AF XY: 0.0909 AC XY: 6741 AN XY: 74142

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0869

Alfa AF: 0.0762 Hom.: 80

Bravo AF: 0.101

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 11, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs73305543; hg19: chr12-32716845;