Variant 1-93532952-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164473.3(FNBP1L):c.670A>G(p.Ile224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,611,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FNBP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056501716).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 link	c.670A>G	p.Ile224Val	missense_variant	8/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 link	c.670A>G	p.Ile224Val	missense_variant	8/14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 link	c.670A>G	p.Ile224Val	missense_variant	8/15		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 link	c.670A>G	p.Ile224Val	missense_variant	8/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 link	c.670A>G	p.Ile224Val	missense_variant	8/14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 link	c.670A>G	p.Ile224Val	missense_variant	8/15	5		ENSP00000359275.2	Q5T0N5-3
FNBP1L	ENST00000424449.2 link	c.205A>G	p.Ile69Val	missense_variant	3/12	2		ENSP00000397451.2	A0A075B6Q2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

247992

Hom.:

AF XY:

0.0000743

AC XY:

AN XY:

134506

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.000352

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000977

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000754

AC:

110

AN:

1459456

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000792

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000807

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000273

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.670A>G (p.I224V) alteration is located in exon 8 (coding exon 8) of the FNBP1L gene. This alteration results from a A to G substitution at nucleotide position 670, causing the isoleucine (I) at amino acid position 224 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.4

DANN

Benign

0.73

DEOGEN2

Benign

0.036

T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.27

T;T;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.3

N;N;.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.62

N;N;.;N

REVEL

Benign

0.089

Sift

Benign

0.37

T;T;.;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.24

MVP

0.10

MPC

0.31

ClinPred

0.016

GERP RS

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.015

gMVP

0.13

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

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