6-109721359-G-C

Position:

• chr6-109721359-G-C

Variant summary

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

The NM_014845.6(FIG4):​c.289+4791G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 151,956 control chromosomes in the GnomAD database, including 48,478 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 0.80 (48478 hom., cov: 29)
• Consequence: FIG4 NM_014845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

Genes affected

FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIG4	NM_014845.6	c.289+4791G>C		intron_variant		ENST00000230124.8
FIG4	XM_011536281.4	c.226+4791G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIG4	ENST00000230124.8	c.289+4791G>C		intron_variant		1	NM_014845.6	P4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121012 AN: 151838 Hom.: 48419 Cov.: 29

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.797 AC: 121136 AN: 151956 Hom.: 48478 Cov.: 29 AF XY: 0.795 AC XY: 59008 AN XY: 74252

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.782

Alfa AF: 0.718 Hom.: 2388

Bravo AF: 0.800

Asia WGS AF: 0.711 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.65

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: rs7764711; hg19: chr6-110042562;