chr11-65884579-G-A

Variant names:

• chr11-65884579-G-A
• rs116455583
• NM_004214.5:c.897C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004214.5(FIBP):​c.897C>T​(p.Leu299Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,614,174 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (3 hom.)
• Consequence: FIBP NM_004214.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.20

Genes affected

FIBP (HGNC:3705): (FGF1 intracellular binding protein) Acidic fibroblast growth factor is mitogenic for a variety of different cell types and acts by stimulating mitogenesis or inducing morphological changes and differentiation. The FIBP protein is an intracellular protein that binds selectively to acidic fibroblast growth factor (aFGF). It is postulated that FIBP may be involved in the mitogenic action of aFGF. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-65884579-G-A is Benign according to our data. Variant chr11-65884579-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 784194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.2 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5	c.897C>T	p.Leu299Leu	synonymous_variant	Exon 8 of 10	ENST00000357519.9	NP_004205.2
FIBP	NM_198897.2	c.918C>T	p.Leu306Leu	synonymous_variant	Exon 8 of 10		NP_942600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9	c.897C>T	p.Leu299Leu	synonymous_variant	Exon 8 of 10	1	NM_004214.5	ENSP00000350124.5

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 415 AN: 152180 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000815 AC: 205 AN: 251454 AF XY: 0.000625

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000401 AC: 586 AN: 1461876 Hom.: 3 Cov.: 34 AF XY: 0.000364 AC XY: 265 AN XY: 727240

Gnomad4 AFR exome AF: 0.0100 AC: 335 AN: 33480

Gnomad4 AMR exome AF: 0.000335 AC: 15 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.000403 AC: 16 AN: 39700

Gnomad4 SAS exome AF: 0.000568 AC: 49 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53414

Gnomad4 NFE exome AF: 0.000126 AC: 140 AN: 1112002

Gnomad4 Remaining exome AF: 0.000497 AC: 30 AN: 60394

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152298 Hom.: 2 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74470

Gnomad4 AFR AF: 0.00944 AC: 0.00943623 AN: 0.00943623

Gnomad4 AMR AF: 0.000523 AC: 0.000522671 AN: 0.000522671

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000578 AC: 0.000578481 AN: 0.000578481

Gnomad4 SAS AF: 0.000414 AC: 0.000414079 AN: 0.000414079

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117606 AN: 0.000117606

Gnomad4 OTH AF: 0.00142 AC: 0.00141911 AN: 0.00141911

Alfa AF: 0.00113 Hom.: 2

Bravo AF: 0.00323

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FIBP: BP4, BP7 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FIBP-related disorder Benign:1

Jan 18, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.57
DANN	Benign	0.89
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

Publications

LitVar

Other links and lift over

dbSNP: rs116455583; hg19: chr11-65652050;