NM_000507.4:c.*21C>T

Variant names:

• chr9-94603360-G-A
• rs9695
• NM_000507.4:c.*21C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000507.4(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 NM_000507.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.05
• Publications: 17 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 -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 rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.*21C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.*21C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001121100.1
FBP1	XM_006717005.5	c.*21C>T		3_prime_UTR_variant	Exon 7 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.*21C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_000507.4	ENSP00000364475.5

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

GnomAD2 exomes AF: 0.515 AC: 125573 AN: 243660 AF XY: 0.509

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 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

African (AFR) AF: 0.495 AC: 16467 AN: 33270

American (AMR) AF: 0.695 AC: 30661 AN: 44102

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 17099 AN: 25994

East Asian (EAS) AF: 0.391 AC: 15428 AN: 39476

South Asian (SAS) AF: 0.435 AC: 37144 AN: 85370

European-Finnish (FIN) AF: 0.425 AC: 22621 AN: 53172

Middle Eastern (MID) AF: 0.539 AC: 3004 AN: 5572

European-Non Finnish (NFE) AF: 0.504 AC: 556662 AN: 1104912

Other (OTH) AF: 0.522 AC: 31309 AN: 60016

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

African (AFR) AF: 0.490 AC: 20287 AN: 41442

American (AMR) AF: 0.634 AC: 9674 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2357 AN: 3464

East Asian (EAS) AF: 0.413 AC: 2125 AN: 5146

South Asian (SAS) AF: 0.432 AC: 2077 AN: 4804

European-Finnish (FIN) AF: 0.418 AC: 4411 AN: 10558

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35020 AN: 67960

Other (OTH) AF: 0.540 AC: 1135 AN: 2102

Alfa AF: 0.523 Hom.: 60273

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

Jun 29, 2018

GeneDx

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

- -

Fructose-biphosphatase deficiency Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-1.1
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: rs9695; hg19: chr9-97365642; COSMIC: COSV64688882; COSMIC: COSV64688882;