Variant rs9481003 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000230124.8(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
ENST00000230124.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.14

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

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 ClinVar 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/exons	MANE	Protein	UniProt
FIG4	NM_014845.6 linkuse as main transcript	c.1271+32G>A		intron_variant		ENST00000230124.8	NP_055660.1
FIG4	XM_011536281.4 linkuse as main transcript	c.1208+32G>A		intron_variant			XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 linkuse as main transcript	c.1271+32G>A		intron_variant		1	NM_014845.6	ENSP00000230124	P4

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

GnomAD3 exomes

AF:

0.114

AC:

28519

AN:

250642

Hom.:

2940

AF XY:

0.106

AC XY:

14364

AN XY:

135528

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 SAS exome

AF:

0.107

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

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.296

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0371

Gnomad4 OTH exome

AF:

0.0911

GnomAD4 genome

AF:

0.163

AC:

24844

AN:

151980

Hom.:

3699

Cov.:

AF XY:

0.166

AC XY:

12341

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.0934

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.0641

Hom.:

1359

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.051

DANN

Benign

0.38

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