3-14873458-A-G

Variant summary

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

The NM_152536.4(FGD5):c.2659-7114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,166 control chromosomes in the GnomAD database, including 1,912 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 0.14 (1912 hom., cov: 32)
• Consequence: FGD5 NM_152536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

Genes affected

FGD5 (HGNC:19117): (FYVE, RhoGEF and PH domain containing 5) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in several processes, including filopodium assembly; regulation of GTPase activity; and regulation of cell shape. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD5	NM_152536.4	c.2659-7114A>G		intron_variant		ENST00000285046.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD5	ENST00000285046.10	c.2659-7114A>G		intron_variant		1	NM_152536.4	P1
FGD5	ENST00000543601.5	c.1936-7114A>G		intron_variant		1
FGD5	ENST00000457774.1	c.298+9198A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21852 AN: 152048 Hom.: 1901 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.144 AC: 21893 AN: 152166 Hom.: 1912 Cov.: 32 AF XY: 0.149 AC XY: 11069 AN XY: 74390

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.159

Alfa AF: 0.141 Hom.: 269

Bravo AF: 0.150

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.9
Dann	Benign	0.71

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: rs17040460; hg19: chr3-14914965;