Variant rs74015090 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 NM_004960.4(FUS):c.524-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,594,272 control chromosomes in the GnomAD database, including 1,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.048 ( 555 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 517 hom. )

Consequence

FUS
NM_004960.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

FUS (HGNC:4010): (FUS RNA binding protein) This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6. [provided by RefSeq, Sep 2009]

FUS links:

FUS (HGNC:):

FUS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-31184918-T-C is Benign according to our data. Variant chr16-31184918-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 259599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUS	NM_004960.4 linkuse as main transcript	c.524-21T>C		intron_variant		ENST00000254108.12	NP_004951.1	P35637-1Q6IBQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUS	ENST00000254108.12 linkuse as main transcript	c.524-21T>C		intron_variant		1	NM_004960.4	ENSP00000254108.8		P35637-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7237

AN:

151844

Hom.:

551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00955

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0148

AC:

3662

AN:

247732

Hom.:

227

AF XY:

0.0118

AC XY:

1585

AN XY:

134168

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00815

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.00706

AC:

10188

AN:

1442312

Hom.:

517

Cov.:

AF XY:

0.00674

AC XY:

4844

AN XY:

718480

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.000462

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00837

Gnomad4 FIN exome

AF:

0.000358

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0479

AC:

7275

AN:

151960

Hom.:

555

Cov.:

AF XY:

0.0458

AC XY:

3406

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00956

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0377

Hom.:

Bravo

AF:

0.0536

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.79

DANN

Benign

0.28

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