Genetic Variant NM_003902.5:c.1801A>C (chr1-77949280-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003902.5(FUBP1):c.1801A>C(p.Thr601Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T601A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FUBP1
NM_003902.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051936537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003902.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FUBP1	NM_003902.5	MANE Select	c.1801A>C	p.Thr601Pro	missense	Exon 19 of 20	NP_003893.2
FUBP1	NM_001410804.1		c.1861A>C	p.Thr621Pro	missense	Exon 20 of 22	NP_001397733.1
FUBP1	NM_001376056.1		c.1798A>C	p.Thr600Pro	missense	Exon 19 of 21	NP_001362985.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FUBP1	ENST00000370768.7	TSL:1 MANE Select	c.1801A>C	p.Thr601Pro	missense	Exon 19 of 20	ENSP00000359804.2
FUBP1	ENST00000294623.8	TSL:1	n.1798A>C		non_coding_transcript_exon	Exon 19 of 21	ENSP00000294623.4
FUBP1	ENST00000421641.2	TSL:5	c.1861A>C	p.Thr621Pro	missense	Exon 20 of 22	ENSP00000402630.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111766

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.070

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.44

M_CAP

Benign

0.0048

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

PhyloP100

1.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.11

REVEL

Benign

0.061

Sift

Benign

0.52

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.31

MVP

0.26

MPC

0.78

ClinPred

0.042

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.15

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over