1-93523357-G-A

Position:

chr1-93523357-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001164473.3(FNBP1L):c.208G>A(p.Val70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,603,658 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.628

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07791114).

BP6

Variant 1-93523357-G-A is Benign according to our data. Variant chr1-93523357-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2521848.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/15		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	4/15	5		ENSP00000359275.2	Q5T0N5-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152192

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000855

AC:

AN:

234008

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126218

show subpopulations

Gnomad AFR exome

AF:

0.0000676

Gnomad AMR exome

AF:

0.00

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:

0.00000943

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451466

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

720812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.049

T;.;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.078

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

N;N;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.45

N;N;.;N

REVEL

Benign

0.046

Sift

Benign

0.27

T;T;.;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.11

MutPred

0.46

Loss of phosphorylation at T67 (P = 0.0903);Loss of phosphorylation at T67 (P = 0.0903);Loss of phosphorylation at T67 (P = 0.0903);Loss of phosphorylation at T67 (P = 0.0903);

MVP

0.14

MPC

0.30

ClinPred

0.064

GERP RS

2.3

Varity_R

0.017

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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