Variant chr1-15765205-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 NM_017556.4(FBLIM1):c.222G>A(p.Pro74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,613,526 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 35 hom., cov: 31)

Exomes 𝑓: 0.0037 ( 70 hom. )

Consequence

FBLIM1
NM_017556.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.20

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=-0.77).

BP6

Variant 1-15765205-G-A is Benign according to our data. Variant chr1-15765205-G-A is described in ClinVar as [Benign]. Clinvar id is 775515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2147/152234) while in subpopulation AFR AF= 0.0425 (1764/41538). AF 95% confidence interval is 0.0408. There are 35 homozygotes in gnomad4. There are 1038 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLIM1	NM_017556.4 linkuse as main transcript	c.222G>A	p.Pro74=	synonymous_variant	3/9	ENST00000375766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLIM1	ENST00000375766.8 linkuse as main transcript	c.222G>A	p.Pro74=	synonymous_variant	3/9	2	NM_017556.4	P1	Q8WUP2-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2139

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00387

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00675

AC:

1660

AN:

245890

Hom.:

AF XY:

0.00664

AC XY:

889

AN XY:

133916

show subpopulations

Gnomad AFR exome

AF:

0.0435

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00572

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.00465

GnomAD4 exome

AF:

0.00371

AC:

5420

AN:

1461292

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

2905

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00958

Gnomad4 EAS exome

AF:

0.00514

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.0141

AC:

2147

AN:

152234

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1038

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00388

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00833

Hom.:

Bravo

AF:

0.0155

EpiCase

AF:

0.00322

EpiControl

AF:

0.00285

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.68

DANN

Benign

0.40

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