Variant chr1-15767505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017556.4(FBLIM1):c.380C>T(p.Ala127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,316,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FBLIM1
NM_017556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0260

Variant links:

Genes affected

FBLIM1 (HGNC:24686): (filamin binding LIM protein 1) This gene encodes a protein with an N-terminal filamin-binding domain, a central proline-rich domain, and, multiple C-terminal LIM domains. This protein localizes at cell junctions and may link cell adhesion structures to the actin cytoskeleton. This protein may be involved in the assembly and stabilization of actin-filaments and likely plays a role in modulating cell adhesion, cell morphology and cell motility. This protein also localizes to the nucleus and may affect cardiomyocyte differentiation after binding with the CSX/NKX2-5 transcription factor. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FBLIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04851666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLIM1	NM_017556.4 linkuse as main transcript	c.380C>T	p.Ala127Val	missense_variant	4/9	ENST00000375766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLIM1	ENST00000375766.8 linkuse as main transcript	c.380C>T	p.Ala127Val	missense_variant	4/9	2	NM_017556.4	P1	Q8WUP2-1

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

134158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000221

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:

0.0000246

AC:

AN:

162738

Hom.:

AF XY:

0.0000111

AC XY:

AN XY:

89922

show subpopulations

Gnomad AFR exome

AF:

0.000112

Gnomad AMR exome

AF:

0.0000925

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:

0.0000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1181810

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

584322

show subpopulations

Gnomad4 AFR exome

AF:

0.000266

Gnomad4 AMR exome

AF:

0.0000722

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:

0.00000845

Gnomad4 OTH exome

AF:

0.0000462

GnomAD4 genome

AF:

0.0000596

AC:

AN:

134222

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

64062

show subpopulations

Gnomad4 AFR

AF:

0.000221

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:

0.0000408

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.380C>T (p.A127V) alteration is located in exon 3 (coding exon 2) of the FBLIM1 gene. This alteration results from a C to T substitution at nucleotide position 380, causing the alanine (A) at amino acid position 127 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0095

T;T;T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.63

.;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.31

T;T;D;T

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.071

MVP

0.56

MPC

0.23

ClinPred

0.019

GERP RS

-0.71

Varity_R

0.031

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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