chr12-32564014-GGGGAGA-G

Position:

• chr12-32564014-GGGGAGA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370298.3(FGD4):​c.167-111_167-106del variant causes a intron change. The variant allele was found at a frequency of 0.106 in 898,300 control chromosomes in the GnomAD database, including 6,362 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (993 hom., cov: 0)
  • Exomes 𝑓: 0.11 (5369 hom.)
• 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 -10 ACMG points.

• BP6: Variant 12-32564014-GGGGAGA-G is Benign according to our data. Variant chr12-32564014-GGGGAGA-G is described in ClinVar as [Benign]. Clinvar id is 1262570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD4	NM_001370298.3	c.167-111_167-106del		intron_variant		ENST00000534526.7	NP_001357227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGD4	ENST00000534526.7	c.167-111_167-106del		intron_variant		5	NM_001370298.3	ENSP00000449273

Frequencies

GnomAD3 genomes AF: 0.103 AC: 14812 AN: 143508 Hom.: 989 Cov.: 0

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.107 AC: 80400 AN: 754702 Hom.: 5369 AF XY: 0.105 AC XY: 40348 AN XY: 383760

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.0932

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.0710

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.103 AC: 14836 AN: 143598 Hom.: 993 Cov.: 0 AF XY: 0.0992 AC XY: 6911 AN XY: 69702

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0244 Hom.: 21

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

Feb 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371242429; hg19: chr12-32716948;