Genetic Variant ENST00000441801.6:c.922G>T (chr1-15774828-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000441801.6(FBLIM1):c.922G>T(p.Ala308Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,988 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 8 hom., cov: 31)

Exomes 𝑓: 0.00066 ( 12 hom. )

Consequence

FBLIM1
ENST00000441801.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.196

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046181977).

BP6

Variant 1-15774828-G-T is Benign according to our data. Variant chr1-15774828-G-T is described in ClinVar as [Benign]. Clinvar id is 780215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00639 (973/152278) while in subpopulation AFR AF= 0.0223 (925/41552). AF 95% confidence interval is 0.0211. There are 8 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLIM1	NM_017556.4 link	c.890+32G>T		intron_variant	Intron 7 of 8	ENST00000375766.8	NP_060026.2	Q8WUP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLIM1	ENST00000375766.8 link	c.890+32G>T		intron_variant	Intron 7 of 8	2	NM_017556.4	ENSP00000364921.3		Q8WUP2-1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

974

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00156

AC:

390

AN:

250494

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000662

AC:

968

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00639

AC:

973

AN:

152278

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

467

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00100

Hom.:

Bravo

AF:

0.00736

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0197

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00193

AC:

234

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 14, 2017

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_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.8

DANN

Benign

0.79

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.78

REVEL

Benign

0.055

Sift

Benign

0.25

Sift4G

Benign

0.21

Polyphen

0.10

Vest4

0.14

MVP

0.37

MPC

0.21

ClinPred

0.0044

GERP RS

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.21

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