rs7315682

Positions:

• chr12-32533023-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370298.3(FGD4):​c.167-31114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,094 control chromosomes in the GnomAD database, including 8,138 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (8138 hom., cov: 32)
• Consequence: FGD4 NM_001370298.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD4	NM_001370298.3	c.167-31114C>T		intron_variant		ENST00000534526.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD4	ENST00000534526.7	c.167-31114C>T		intron_variant		5	NM_001370298.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39579 AN: 151976 Hom.: 8106 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.261 AC: 39660 AN: 152094 Hom.: 8138 Cov.: 32 AF XY: 0.257 AC XY: 19081 AN XY: 74334

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.219

Alfa AF: 0.167 Hom.: 4009

Bravo AF: 0.275

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.23

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: rs7315682; hg19: chr12-32685957;