rs777259406

Variant names:

• chr1-77962884-T-A
• rs777259406
• NM_003902.5:c.1230A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-77962884-T-A
• chr1-77962884-T-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003902.5(FUBP1):​c.1230A>T​(p.Ile410Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUBP1 NM_003902.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.87 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUBP1	NM_003902.5	MANE Select	c.1230A>T	p.Ile410Ile	synonymous	Exon 14 of 20	NP_003893.2
	FUBP1	NM_001410804.1		c.1290A>T	p.Ile430Ile	synonymous	Exon 15 of 22	NP_001397733.1	C9JSZ1
	FUBP1	NM_001376056.1		c.1227A>T	p.Ile409Ile	synonymous	Exon 14 of 21	NP_001362985.1	A0A994J3Q8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUBP1	ENST00000370768.7	TSL:1 MANE Select	c.1230A>T	p.Ile410Ile	synonymous	Exon 14 of 20	ENSP00000359804.2	Q96AE4-1
	FUBP1	ENST00000294623.8	TSL:1	n.1227A>T		non_coding_transcript_exon	Exon 14 of 21	ENSP00000294623.4	Q96AE4-2
	FUBP1	ENST00000421641.2	TSL:5	c.1290A>T	p.Ile430Ile	synonymous	Exon 15 of 22	ENSP00000402630.2	C9JSZ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		2.9
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs777259406; hg19: chr1-78428569;