rs9481003

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014845.6(FIG4):c.1271+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,589,434 control chromosomes in the GnomAD database, including 10,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3699 hom., cov: 32)

Exomes 𝑓: 0.066 ( 7032 hom. )

Consequence

FIG4
NM_014845.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.14

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
Charcot-Marie-Tooth disease type 4J
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine
Yunis-Varon syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
amyotrophic lateral sclerosis type 11
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
bilateral parasagittal parieto-occipital polymicrogyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FIG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-109760415-G-A is Benign according to our data. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109760415-G-A is described in CliVar as Benign. Clinvar id is 260445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6 link	c.1271+32G>A		intron_variant	Intron 11 of 22	ENST00000230124.8	NP_055660.1	Q92562
FIG4	XM_011536281.4 link	c.1208+32G>A		intron_variant	Intron 11 of 22		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 link	c.1271+32G>A		intron_variant	Intron 11 of 22	1	NM_014845.6	ENSP00000230124.4		Q92562

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24786

AN:

151862

Hom.:

3690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.0941

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.114

AC:

28519

AN:

250642

AF XY:

0.106

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0830

GnomAD4 exome

AF:

0.0660

AC:

94827

AN:

1437454

Hom.:

7032

Cov.:

AF XY:

0.0663

AC XY:

47519

AN XY:

716804

show subpopulations

African (AFR)

AF:

0.393

AC:

12779

AN:

32558

American (AMR)

AF:

0.129

AC:

5785

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3297

AN:

25946

East Asian (EAS)

AF:

0.296

AC:

11705

AN:

39490

South Asian (SAS)

AF:

0.106

AC:

9059

AN:

85668

European-Finnish (FIN)

AF:

0.110

AC:

5760

AN:

52586

Middle Eastern (MID)

AF:

0.0937

AC:

536

AN:

5718

European-Non Finnish (NFE)

AF:

0.0371

AC:

40489

AN:

1091330

Other (OTH)

AF:

0.0911

AC:

5417

AN:

59478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3813

7625

11438

15250

19063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1908

3816

5724

7632

9540

<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:

0.163

AC:

24844

AN:

151980

Hom.:

3699

Cov.:

AF XY:

0.166

AC XY:

12341

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.387

AC:

16042

AN:

41410

American (AMR)

AF:

0.137

AC:

2096

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

438

AN:

3468

East Asian (EAS)

AF:

0.276

AC:

1423

AN:

5162

South Asian (SAS)

AF:

0.0934

AC:

449

AN:

4808

European-Finnish (FIN)

AF:

0.119

AC:

1254

AN:

10550

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0397

AC:

2697

AN:

67984

Other (OTH)

AF:

0.150

AC:

317

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

886

1772

2658

3544

4430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.0840

Hom.:

4181

Bravo

AF:

0.175

Asia WGS

AF:

0.191

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 26, 2018

GeneDx

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

-0.81

CADD

Benign

0.051

(source)

DANN

Benign

0.38

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over