NM_003837.4:c.675T>C

Variant names:

• chr9-94567300-A-G
• rs111617337
• NM_003837.4:c.675T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003837.4(FBP2):​c.675T>C​(p.Thr225Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,614,134 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (131 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (120 hom.)
• Consequence: FBP2 NM_003837.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95
• Publications: 1 publications found

Genes affected

FBP2 (HGNC:3607): (fructose-bisphosphatase 2) This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 9-94567300-A-G is Benign according to our data. Variant chr9-94567300-A-G is described in ClinVar as Benign. ClinVar VariationId is 776436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003837.4. 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
	FBP2	NM_003837.4	MANE Select	c.675T>C	p.Thr225Thr	synonymous	Exon 5 of 7	NP_003828.2
	PCAT7	NR_121567.3	MANE Select	n.448-90A>G		intron	N/A
	PCAT7	NR_121566.3		n.533-90A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP2	ENST00000375337.4	TSL:1 MANE Select	c.675T>C	p.Thr225Thr	synonymous	Exon 5 of 7	ENSP00000364486.3	O00757
	PCAT7	ENST00000644721.3	MANE Select	n.448-90A>G		intron	N/A
	PCAT7	ENST00000452148.4	TSL:2	n.462-90A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3416 AN: 152138 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00612 AC: 1538 AN: 251478 AF XY: 0.00455

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000466

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00262 AC: 3828 AN: 1461878 Hom.: 120 Cov.: 32 AF XY: 0.00231 AC XY: 1677 AN XY: 727238

African (AFR) AF: 0.0790 AC: 2644 AN: 33478

American (AMR) AF: 0.00470 AC: 210 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.000521 AC: 579 AN: 1112004

Other (OTH) AF: 0.00560 AC: 338 AN: 60396

GnomAD4 genome AF: 0.0225 AC: 3428 AN: 152256 Hom.: 131 Cov.: 32 AF XY: 0.0218 AC XY: 1622 AN XY: 74454

African (AFR) AF: 0.0776 AC: 3224 AN: 41548

American (AMR) AF: 0.00856 AC: 131 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68020

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.0114 Hom.: 39

Bravo AF: 0.0253

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.57
DANN	Benign	0.71
PhyloP100		-1.9
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs111617337; hg19: chr9-97329582;