rs10499054

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014845.6(FIG4):c.1948+3A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.598 in 1,518,784 control chromosomes in the GnomAD database, including 287,180 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21481 hom., cov: 32)

Exomes 𝑓: 0.61 ( 265699 hom. )

Consequence

FIG4
NM_014845.6 splice_region, intron

Scores

Splicing: ADA: 0.04755

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 4.54

Variant links:

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]

FIG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 6-109785031-A-G is Benign according to our data. Variant chr6-109785031-A-G is described in ClinVar as [Benign]. Clinvar id is 260447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109785031-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6 link	c.1948+3A>G		splice_region_variant, intron_variant	Intron 17 of 22	ENST00000230124.8	NP_055660.1	Q92562
FIG4	XM_011536281.4 link	c.1885+3A>G		splice_region_variant, intron_variant	Intron 17 of 22		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 link	c.1948+3A>G		splice_region_variant, intron_variant	Intron 17 of 22	1	NM_014845.6	ENSP00000230124.4		Q92562

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74492

AN:

151876

Hom.:

21490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.528

AC:

132285

AN:

250486

AF XY:

0.533

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.610

AC:

833467

AN:

1366790

Hom.:

265699

Cov.:

AF XY:

0.604

AC XY:

414332

AN XY:

685482

show subpopulations

Gnomad4 AFR exome

AF:

0.173

AC:

5618

AN:

32450

Gnomad4 AMR exome

AF:

0.448

AC:

19913

AN:

44414

Gnomad4 ASJ exome

AF:

0.555

AC:

14118

AN:

25454

Gnomad4 EAS exome

AF:

0.318

AC:

12492

AN:

39248

Gnomad4 SAS exome

AF:

0.361

AC:

30473

AN:

84526

Gnomad4 FIN exome

AF:

0.567

AC:

30024

AN:

52940

Gnomad4 NFE exome

AF:

0.669

AC:

685925

AN:

1024822

Gnomad4 Remaining exome

AF:

0.566

AC:

32437

AN:

57342

Heterozygous variant carriers

12427

24854

37281

49708

62135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

16720

33440

50160

66880

83600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.490

AC:

74484

AN:

151994

Hom.:

21481

Cov.:

AF XY:

0.480

AC XY:

35659

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.195

AC:

0.195251

AN:

0.195251

Gnomad4 AMR

AF:

0.508

AC:

0.507525

AN:

0.507525

Gnomad4 ASJ

AF:

0.569

AC:

0.568667

AN:

0.568667

Gnomad4 EAS

AF:

0.327

AC:

0.327199

AN:

0.327199

Gnomad4 SAS

AF:

0.349

AC:

0.348692

AN:

0.348692

Gnomad4 FIN

AF:

0.543

AC:

0.542797

AN:

0.542797

Gnomad4 NFE

AF:

0.674

AC:

0.673619

AN:

0.673619

Gnomad4 OTH

AF:

0.516

AC:

0.516114

AN:

0.516114

Heterozygous variant carriers

1633

3266

4898

6531

8164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.594

Hom.:

70665

Bravo

AF:

0.478

Asia WGS

AF:

0.313

AC:

1089

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 22, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 22, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Amyotrophic lateral sclerosis type 11

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 4J

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Yunis-Varon syndrome

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bilateral parasagittal parieto-occipital polymicrogyria

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

Mutation Taster

=95/5

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.048

dbscSNV1_RF

Benign

0.14

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over