Variant chr16-31192208-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001170634.1(FUS):c.*770G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 526,328 control chromosomes in the GnomAD database, including 28,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 6043 hom., cov: 31)

Exomes 𝑓: 0.33 ( 22623 hom. )

Consequence

FUS
NM_001170634.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0150

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-31192208-G-C is Benign according to our data. Variant chr16-31192208-G-C is described in ClinVar as [Benign]. Clinvar id is 319004.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
FUS	NM_001170634.1 linkuse as main transcript	c.*770G>C	3_prime_UTR_variant	15/15	NP_001164105.1	P35637-2
FUS	NM_001170937.1 linkuse as main transcript	c.*770G>C	3_prime_UTR_variant	15/15	NP_001164408.1	Q13344
FUS	XM_011545781.2 linkuse as main transcript	c.*770G>C	3_prime_UTR_variant	15/15	XP_011544083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38803

AN:

151904

Hom.:

6041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0788

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.530

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.336

AC:

43057

AN:

128058

Hom.:

8035

AF XY:

0.348

AC XY:

24409

AN XY:

70124

show subpopulations

Gnomad AFR exome

AF:

0.0673

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.251

Gnomad SAS exome

AF:

0.509

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.330

AC:

123567

AN:

374306

Hom.:

22623

Cov.:

AF XY:

0.345

AC XY:

70785

AN XY:

205448

show subpopulations

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.507

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.255

AC:

38812

AN:

152022

Hom.:

6043

Cov.:

AF XY:

0.263

AC XY:

19516

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0786

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.530

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.211

Hom.:

785

Bravo

AF:

0.236

Asia WGS

AF:

0.380

AC:

1320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.4

DANN

Benign

0.78

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