rs2274257

Positions:

chr1-77963723-G-C

Variant summary

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

The NM_003902.5(FUBP1):c.1042-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,592,650 control chromosomes in the GnomAD database, including 7,084 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 834 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6250 hom. )

Consequence

FUBP1
NM_003902.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001518

Clinical Significance

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

Conservation

PhyloP100: -0.0200

Variant links:

Genes affected

FUBP1 (HGNC:4004): (far upstream element binding protein 1) The protein encoded by this gene is a single stranded DNA-binding protein that binds to multiple DNA elements, including the far upstream element (FUSE) located upstream of c-myc. Binding to FUSE occurs on the non-coding strand, and is important to the regulation of c-myc in undifferentiated cells. This protein contains three domains, an amphipathic helix N-terminal domain, a DNA-binding central domain, and a C-terminal transactivation domain that contains three tyrosine-rich motifs. The N-terminal domain is thought to repress the activity of the C-terminal domain. This protein is also thought to bind RNA, and contains 3'-5' helicase activity with in vitro activity on both DNA-DNA and RNA-RNA duplexes. Aberrant expression of this gene has been found in malignant tissues, and this gene is important to neural system and lung development. Binding of this protein to viral RNA is thought to play a role in several viral diseases, including hepatitis C and hand, foot and mouth disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

FUBP1 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=-0.82).

BP6

Variant 1-77963723-G-C is Benign according to our data. Variant chr1-77963723-G-C is described in ClinVar as [Benign]. Clinvar id is 402886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUBP1	NM_003902.5 linkuse as main transcript	c.1042-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370768.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUBP1	ENST00000370768.7 linkuse as main transcript	c.1042-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003902.5	P1	Q96AE4-1

Frequencies

GnomAD3 genomes

AF:

0.0910

AC:

13835

AN:

152070

Hom.:

827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.0927

Gnomad EAS

AF:

0.0862

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.115

AC:

26778

AN:

233514

Hom.:

1987

AF XY:

0.112

AC XY:

14138

AN XY:

126392

show subpopulations

Gnomad AFR exome

AF:

0.0513

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.0889

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.0827

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.0853

AC:

122811

AN:

1440464

Hom.:

6250

Cov.:

AF XY:

0.0860

AC XY:

61627

AN XY:

716734

show subpopulations

Gnomad4 AFR exome

AF:

0.0498

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.0898

Gnomad4 EAS exome

AF:

0.0785

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.0757

Gnomad4 OTH exome

AF:

0.0901

GnomAD4 genome

AF:

0.0911

AC:

13859

AN:

152186

Hom.:

834

Cov.:

AF XY:

0.0979

AC XY:

7283

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0517

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.0927

Gnomad4 EAS

AF:

0.0862

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.0798

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0840

Hom.:

188

Bravo

AF:

0.0910

Asia WGS

AF:

0.121

AC:

418

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

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.64

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.010

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