Genetic Variant FIBP:c.1005-10G>A (chr11-65884053-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004214.5(FIBP):c.1005-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,611,750 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

FIBP
NM_004214.5 intron

Scores

Splicing: ADA: 0.0004652

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

Variant links:

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]

FIBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-65884053-C-T is Benign according to our data. Variant chr11-65884053-C-T is described in ClinVar as [Benign]. Clinvar id is 785815.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5 link	c.1005-10G>A		intron_variant	Intron 9 of 9	ENST00000357519.9	NP_004205.2	O43427-2
FIBP	NM_198897.2 link	c.1026-10G>A		intron_variant	Intron 9 of 9		NP_942600.1	O43427-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9 link	c.1005-10G>A		intron_variant	Intron 9 of 9	1	NM_004214.5	ENSP00000350124.5		O43427-2

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

398

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000727

AC:

179

AN:

246274

AF XY:

0.000653

show subpopulations

Gnomad AFR exome

AF:

0.00756

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.000326

AC:

476

AN:

1459416

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

215

AN XY:

725882

show subpopulations

Gnomad4 AFR exome

AF:

0.00846

AC:

283

AN:

33440

Gnomad4 AMR exome

AF:

0.00132

AC:

AN:

44562

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26038

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39660

Gnomad4 SAS exome

AF:

0.0000117

AC:

AN:

85826

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53338

Gnomad4 NFE exome

AF:

0.0000612

AC:

AN:

1110490

Gnomad4 Remaining exome

AF:

0.00108

AC:

AN:

60296

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152334

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00861

AC:

0.00860949

AN:

0.00860949

Gnomad4 AMR

AF:

0.00209

AC:

0.00209096

AN:

0.00209096

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000441

AC:

0.0000441021

AN:

0.0000441021

Gnomad4 OTH

AF:

0.00331

AC:

0.00331439

AN:

0.00331439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00308

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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

0.12

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over