Variant 1-15774908-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000441801.6(FBLIM1):c.1002G>A(p.Leu334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,595,024 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 12 hom., cov: 31)

Exomes 𝑓: 0.00070 ( 12 hom. )

Consequence

FBLIM1
ENST00000441801.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.776

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-15774908-G-A is Benign according to our data. Variant chr1-15774908-G-A is described in ClinVar as [Benign]. Clinvar id is 786981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.776 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1113/151834) while in subpopulation AFR AF= 0.0257 (1062/41394). AF 95% confidence interval is 0.0244. There are 12 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLIM1	NM_017556.4 linkuse as main transcript	c.890+112G>A		intron_variant		ENST00000375766.8	NP_060026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLIM1	ENST00000441801.6 linkuse as main transcript	c.1002G>A	p.Leu334=	synonymous_variant	6/6	1		ENSP00000416387		Q8WUP2-2
FBLIM1	ENST00000375766.8 linkuse as main transcript	c.890+112G>A		intron_variant		2	NM_017556.4	ENSP00000364921	P1	Q8WUP2-1
FBLIM1	ENST00000375771.5 linkuse as main transcript	c.890+112G>A		intron_variant		1		ENSP00000364926	P1	Q8WUP2-1
FBLIM1	ENST00000332305.5 linkuse as main transcript	c.599+112G>A		intron_variant		2		ENSP00000364920		Q8WUP2-3

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1114

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00186

AC:

393

AN:

211456

Hom.:

AF XY:

0.00138

AC XY:

159

AN XY:

114846

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000696

AC:

1004

AN:

1443190

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

432

AN XY:

716590

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00733

AC:

1113

AN:

151834

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

535

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00276

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00808

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.3

DANN

Benign

0.56

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