rs2273752

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014845.6(FIG4):c.647-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,579,074 control chromosomes in the GnomAD database, including 113,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.34 ( 9275 hom., cov: 32)

Exomes 𝑓: 0.38 ( 104109 hom. )

Consequence

FIG4
NM_014845.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.200

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-109738307-C-A is Benign according to our data. Variant chr6-109738307-C-A is described in ClinVar as [Benign]. Clinvar id is 260451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109738307-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6 link	c.647-18C>A		intron_variant	Intron 6 of 22	ENST00000230124.8	NP_055660.1	Q92562
FIG4	XM_011536281.4 link	c.584-18C>A		intron_variant	Intron 6 of 22		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 link	c.647-18C>A		intron_variant	Intron 6 of 22	1	NM_014845.6	ENSP00000230124.4		Q92562

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51244

AN:

151660

Hom.:

9271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.391

AC:

97958

AN:

250508

Hom.:

19875

AF XY:

0.397

AC XY:

53733

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.378

AC:

539988

AN:

1427296

Hom.:

104109

Cov.:

AF XY:

0.382

AC XY:

271824

AN XY:

711978

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.420

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.338

AC:

51273

AN:

151778

Hom.:

9275

Cov.:

AF XY:

0.342

AC XY:

25335

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.365

Hom.:

2329

Bravo

AF:

0.332

Asia WGS

AF:

0.422

AC:

1465

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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

-0.74

CADD

Benign

DANN

Benign

0.79

BranchPoint Hunter

1.0

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

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