1-77968172-T-G

Variant names:

• chr1-77968172-T-G
• rs138606412
• NM_003902.5:c.243A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003902.5(FUBP1):​c.243A>C​(p.Gln81His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,536,358 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (3 hom.)
• Consequence: FUBP1 NM_003902.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0410
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00651592).
• BS2: High AC in GnomAd4 at 261 AD gene.

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.243A>C	p.Gln81His	missense	Exon 3 of 20	NP_003893.2
	FUBP1	NM_001410804.1		c.306A>C	p.Gln102His	missense	Exon 4 of 22	NP_001397733.1	C9JSZ1
	FUBP1	NM_001376056.1		c.243A>C	p.Gln81His	missense	Exon 3 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.243A>C	p.Gln81His	missense	Exon 3 of 20	ENSP00000359804.2	Q96AE4-1
	FUBP1	ENST00000294623.8	TSL:1	n.243A>C		non_coding_transcript_exon	Exon 3 of 21	ENSP00000294623.4	Q96AE4-2
	FUBP1	ENST00000421641.2	TSL:5	c.306A>C	p.Gln102His	missense	Exon 4 of 22	ENSP00000402630.2	C9JSZ1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000473 AC: 88 AN: 186060 AF XY: 0.000233

Gnomad AFR exome AF: 0.00675

Gnomad AMR exome AF: 0.000305

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000242

GnomAD4 exome AF: 0.000148 AC: 205 AN: 1384050 Hom.: 3 Cov.: 26 AF XY: 0.000129 AC XY: 89 AN XY: 689300

African (AFR) AF: 0.00616 AC: 171 AN: 27754

American (AMR) AF: 0.000269 AC: 7 AN: 26054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23692

East Asian (EAS) AF: 0.00 AC: 0 AN: 35254

South Asian (SAS) AF: 0.00 AC: 0 AN: 75696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52870

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5556

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1080082

Other (OTH) AF: 0.000385 AC: 22 AN: 57092

GnomAD4 genome AF: 0.00171 AC: 261 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74470

African (AFR) AF: 0.00608 AC: 253 AN: 41590

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000624 Hom.: 3

Bravo AF: 0.00208

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000659 AC: 80

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.041
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.083
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.14	B
Vest4		0.42
MutPred		0.29		Gain of loop (P = 0.0045)
MVP		0.51
MPC		1.5
ClinPred		0.074	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.50
Mutation Taster		=83/17	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: rs138606412; hg19: chr1-78433856;