Variant 17-18245651-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002018.4(FLII):c.3513C>T(p.Asn1171Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,613,670 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

FLII
NM_002018.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.961

Variant links:

Genes affected

FLII (HGNC:3750): (FLII actin remodeling protein) This gene encodes a protein with a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat-protein protein interaction domain. The protein is similar to a Drosophila protein involved in early embryogenesis and the structural organization of indirect flight muscle. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

FLII links:

FLII (HGNC:):

FLII links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-18245651-G-A is Benign according to our data. Variant chr17-18245651-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.961 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLII	NM_002018.4 linkuse as main transcript	c.3513C>T	p.Asn1171Asn	synonymous_variant	28/30	ENST00000327031.9	NP_002009.1	Q13045-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLII	ENST00000327031.9 linkuse as main transcript	c.3513C>T	p.Asn1171Asn	synonymous_variant	28/30	1	NM_002018.4	ENSP00000324573.4		Q13045-1

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00142

AC:

356

AN:

251192

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00150

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00128

AC:

1870

AN:

1461456

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

985

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.00769

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152214

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	FLII: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely 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

-0.80

CADD

Benign

0.023

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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