chr9-94603260-A-C

Variant names:

• chr9-94603260-A-C
• rs2274689
• NM_000507.4:c.*121T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000507.4(FBP1):​c.*121T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 833,908 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.013 (25 hom., cov: 33)
  • Exomes 𝑓: 0.018 (162 hom.)
• Consequence: FBP1 NM_000507.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.254
• Publications: 5 publications found

Genes affected

FBP1 (HGNC:3606): (fructose-bisphosphatase 1) Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis. [provided by RefSeq, Jul 2008]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-94603260-A-C is Benign according to our data. Variant chr9-94603260-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 913848.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0132 (2009/152300) while in subpopulation SAS AF = 0.0296 (143/4824). AF 95% confidence interval is 0.0257. There are 25 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000507.4. 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
	FBP1	NM_000507.4	MANE Select	c.*121T>G		3_prime_UTR	Exon 7 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.*121T>G		3_prime_UTR	Exon 8 of 8	NP_001121100.1	P09467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.*121T>G		3_prime_UTR	Exon 7 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.*121T>G		3_prime_UTR	Exon 8 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.*121T>G		3_prime_UTR	Exon 7 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2011 AN: 152182 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.0181 AC: 12349 AN: 681608 Hom.: 162 Cov.: 9 AF XY: 0.0189 AC XY: 6789 AN XY: 360002

African (AFR) AF: 0.00363 AC: 65 AN: 17896

American (AMR) AF: 0.0110 AC: 380 AN: 34664

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 1254 AN: 20432

East Asian (EAS) AF: 0.0391 AC: 1271 AN: 32496

South Asian (SAS) AF: 0.0275 AC: 1766 AN: 64120

European-Finnish (FIN) AF: 0.00551 AC: 267 AN: 48482

Middle Eastern (MID) AF: 0.0219 AC: 59 AN: 2688

European-Non Finnish (NFE) AF: 0.0156 AC: 6637 AN: 426382

Other (OTH) AF: 0.0189 AC: 650 AN: 34448

GnomAD4 genome AF: 0.0132 AC: 2009 AN: 152300 Hom.: 25 Cov.: 33 AF XY: 0.0134 AC XY: 997 AN XY: 74470

African (AFR) AF: 0.00344 AC: 143 AN: 41564

American (AMR) AF: 0.0114 AC: 175 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5180

South Asian (SAS) AF: 0.0296 AC: 143 AN: 4824

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1076 AN: 68026

Other (OTH) AF: 0.0185 AC: 39 AN: 2110

Alfa AF: 0.0174 Hom.: 38

Bravo AF: 0.0125

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Fructose-biphosphatase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		0.25
Mutation Taster		=100/0	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: rs2274689; hg19: chr9-97365542;