3-14866470-C-A

Variant names:

• chr3-14866470-C-A
• rs17040424
• NM_152536.4:c.2658+2210C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152536.4(FGD5):​c.2658+2210C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,054 control chromosomes in the GnomAD database, including 810 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 0.091 (810 hom., cov: 31)
• Consequence: FGD5 NM_152536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGD5	NM_152536.4	c.2658+2210C>A		intron_variant	Intron 2 of 19	ENST00000285046.10	NP_689749.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGD5	ENST00000285046.10	c.2658+2210C>A		intron_variant	Intron 2 of 19	1	NM_152536.4	ENSP00000285046.5
FGD5	ENST00000543601.5	c.1935+2210C>A		intron_variant	Intron 2 of 18	1		ENSP00000445949.1
FGD5	ENST00000457774.1	c.297+2210C>A		intron_variant	Intron 2 of 5	5		ENSP00000394827.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13861 AN: 151938 Hom.: 810 Cov.: 31

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0953

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

GnomAD4 genome AF: 0.0912 AC: 13860 AN: 152054 Hom.: 810 Cov.: 31 AF XY: 0.0913 AC XY: 6782 AN XY: 74314

African (AFR) AF: 0.0611 AC: 2537 AN: 41504

American (AMR) AF: 0.106 AC: 1619 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1562 AN: 5140

South Asian (SAS) AF: 0.0593 AC: 285 AN: 4804

European-Finnish (FIN) AF: 0.0974 AC: 1030 AN: 10574

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0917 AC: 6231 AN: 67984

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0580 Hom.: 69

Bravo AF: 0.0918

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.43
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17040424; hg19: chr3-14907977;