rs72743247

Variant names:

• chr9-94559122-A-G
• rs72743247
• NM_003837.4:c.836T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3 BP4_Strong BP6_Moderate BS2

The NM_003837.4(FBP2):​c.836T>C​(p.Leu279Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,611,416 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (82 hom.)
• Consequence: FBP2 NM_003837.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.72
• Publications: 7 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 -9 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.038577616).
• BP6: Variant 9-94559122-A-G is Benign according to our data. Variant chr9-94559122-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3257644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 754 AD gene.

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.836T>C	p.Leu279Pro	missense	Exon 7 of 7	NP_003828.2
	PCAT7	NR_121567.3	MANE Select	n.417A>G		non_coding_transcript_exon	Exon 2 of 3
	PCAT7	NR_121566.3		n.502A>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP2	ENST00000375337.4	TSL:1 MANE Select	c.836T>C	p.Leu279Pro	missense	Exon 7 of 7	ENSP00000364486.3	O00757
	PCAT7	ENST00000644721.3	MANE Select	n.417A>G		non_coding_transcript_exon	Exon 2 of 3
	PCAT7	ENST00000452148.4	TSL:2	n.431A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 754 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00955

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00497 AC: 1245 AN: 250702 AF XY: 0.00486

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.000841

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.00983

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00936 AC: 13662 AN: 1459110 Hom.: 82 Cov.: 32 AF XY: 0.00901 AC XY: 6538 AN XY: 725456

African (AFR) AF: 0.00141 AC: 47 AN: 33418

American (AMR) AF: 0.00103 AC: 46 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00294 AC: 157 AN: 53386

Middle Eastern (MID) AF: 0.000399 AC: 2 AN: 5016

European-Non Finnish (NFE) AF: 0.0117 AC: 13011 AN: 1110530

Other (OTH) AF: 0.00646 AC: 389 AN: 60228

GnomAD4 genome AF: 0.00495 AC: 754 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00423 AC XY: 315 AN XY: 74484

African (AFR) AF: 0.00159 AC: 66 AN: 41574

American (AMR) AF: 0.00124 AC: 19 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00956 AC: 650 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00792 Hom.: 19

Bravo AF: 0.00500

TwinsUK AF: 0.0138 AC: 51

ALSPAC AF: 0.0117 AC: 45

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00837 AC: 72

ExAC AF: 0.00497 AC: 603

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00812

EpiControl AF: 0.00895

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.039	T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Pathogenic	4.4	H
PhyloP100		8.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MVP		0.95
MPC		0.72
ClinPred		0.15	T
GERP RS		4.3
Varity_R		0.94
gMVP		0.96
Mutation Taster		=60/40	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: rs72743247; hg19: chr9-97321404; COSMIC: COSV64695962;