1-77962911-G-A

Variant names:

• chr1-77962911-G-A
• rs2228247
• NM_003902.5:c.1203C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003902.5(FUBP1):​c.1203C>T​(p.Ser401Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00513 in 1,612,116 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (145 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (193 hom.)
• Consequence: FUBP1 NM_003902.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.14

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-77962911-G-A is Benign according to our data. Variant chr1-77962911-G-A is described in ClinVar as [Benign]. Clinvar id is 783289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUBP1	NM_003902.5	c.1203C>T	p.Ser401Ser	synonymous_variant	Exon 14 of 20	ENST00000370768.7	NP_003893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUBP1	ENST00000370768.7	c.1203C>T	p.Ser401Ser	synonymous_variant	Exon 14 of 20	1	NM_003902.5	ENSP00000359804.2

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4111 AN: 152068 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00696 AC: 1744 AN: 250554 AF XY: 0.00503

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.00398

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00285 AC: 4157 AN: 1459930 Hom.: 193 Cov.: 29 AF XY: 0.00241 AC XY: 1750 AN XY: 726310

Gnomad4 AFR exome AF: 0.102 AC: 3400 AN: 33358

Gnomad4 AMR exome AF: 0.00426 AC: 190 AN: 44608

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26078

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39620

Gnomad4 SAS exome AF: 0.000197 AC: 17 AN: 86090

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53378

Gnomad4 NFE exome AF: 0.000169 AC: 188 AN: 1110744

Gnomad4 Remaining exome AF: 0.00569 AC: 343 AN: 60300

GnomAD4 genome AF: 0.0271 AC: 4117 AN: 152186 Hom.: 145 Cov.: 32 AF XY: 0.0256 AC XY: 1903 AN XY: 74404

Gnomad4 AFR AF: 0.0944 AC: 0.0944187 AN: 0.0944187

Gnomad4 AMR AF: 0.00849 AC: 0.00849451 AN: 0.00849451

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207383 AN: 0.000207383

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000294 AC: 0.0002941 AN: 0.0002941

Gnomad4 OTH AF: 0.0223 AC: 0.022296 AN: 0.022296

Alfa AF: 0.0123 Hom.: 57

Bravo AF: 0.0304

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 08, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.3
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2228247; hg19: chr1-78428596;