rs9695

Positions:

• chr9-94603360-G-A
• chr9-94603360-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375326.9(FBP1):​c.*21C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,603,824 control chromosomes in the GnomAD database, including 206,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20119 hom., cov: 32)
  • Exomes 𝑓: 0.50 (186350 hom.)
• Consequence: FBP1 ENST00000375326.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.05

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-94603360-G-A is Benign according to our data. Variant chr9-94603360-G-A is described in ClinVar as [Benign]. Clinvar id is 256318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.*21C>T		3_prime_UTR_variant	7/7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.*21C>T		3_prime_UTR_variant	8/8		NP_001121100.1
FBP1	XM_006717005.5	c.*21C>T		3_prime_UTR_variant	7/7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.*21C>T		3_prime_UTR_variant	7/7	1	NM_000507.4	ENSP00000364475	P1
PCAT7	ENST00000647389.1	n.1712G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77802 AN: 151822 Hom.: 20105 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.541

GnomAD3 exomes AF: 0.515 AC: 125573 AN: 243660 Hom.: 33412 AF XY: 0.509 AC XY: 67008 AN XY: 131550

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.697

Gnomad ASJ exome AF: 0.658

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.427

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.503 AC: 730395 AN: 1451884 Hom.: 186350 Cov.: 30 AF XY: 0.501 AC XY: 362128 AN XY: 722176

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.391

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.512 AC: 77858 AN: 151940 Hom.: 20119 Cov.: 32 AF XY: 0.509 AC XY: 37766 AN XY: 74234

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.540

Alfa AF: 0.524 Hom.: 36925

Bravo AF: 0.529

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fructose-biphosphatase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.67

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: rs9695; hg19: chr9-97365642; COSMIC: COSV64688882; COSMIC: COSV64688882;