NM_014845.6:c.2547-4600G>C

Variant names:

• chr6-109820488-G-C
• rs4947022
• NM_014845.6:c.2547-4600G>C

Variant summary

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

The NM_014845.6(FIG4):​c.2547-4600G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,780 control chromosomes in the GnomAD database, including 13,967 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 0.41 (13967 hom., cov: 30)
• Consequence: FIG4 NM_014845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6	c.2547-4600G>C		intron_variant	Intron 22 of 22	ENST00000230124.8	NP_055660.1
FIG4	XM_011536281.4	c.2484-4600G>C		intron_variant	Intron 22 of 22		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8	c.2547-4600G>C		intron_variant	Intron 22 of 22	1	NM_014845.6	ENSP00000230124.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62322 AN: 151662 Hom.: 13960 Cov.: 30

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.411 AC: 62348 AN: 151780 Hom.: 13967 Cov.: 30 AF XY: 0.421 AC XY: 31196 AN XY: 74158

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.448

Alfa AF: 0.261 Hom.: 667

Bravo AF: 0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.33

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: rs4947022; hg19: chr6-110141691; COSMIC: COSV57786264;