Genetic Variant FLII:c.1596+69A>G (chr17-18251196-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002018.4(FLII):c.1596+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,535,390 control chromosomes in the GnomAD database, including 42,476 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3883 hom., cov: 33)

Exomes 𝑓: 0.23 ( 38593 hom. )

Consequence

FLII
NM_002018.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

cardiomyopathy, dilated, 2j
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FLII links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002018.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FLII	NM_002018.4	MANE Select	c.1596+69A>G	intron	N/A	NP_002009.1
FLII	NM_001256264.2		c.1563+69A>G	intron	N/A	NP_001243193.1
FLII	NM_001256265.2		c.1431+69A>G	intron	N/A	NP_001243194.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FLII	ENST00000327031.9	TSL:1 MANE Select	c.1596+69A>G	intron	N/A	ENSP00000324573.4
FLII	ENST00000579294.5	TSL:1	c.1563+69A>G	intron	N/A	ENSP00000463534.1
FLII	ENST00000496727.1	TSL:5	n.276A>G	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33450

AN:

151994

Hom.:

3876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.234

AC:

324379

AN:

1383278

Hom.:

38593

Cov.:

AF XY:

0.234

AC XY:

160074

AN XY:

685162

show subpopulations

African (AFR)

AF:

0.152

AC:

4846

AN:

31812

American (AMR)

AF:

0.247

AC:

10121

AN:

40942

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6375

AN:

23660

East Asian (EAS)

AF:

0.262

AC:

10041

AN:

38346

South Asian (SAS)

AF:

0.192

AC:

15278

AN:

79724

European-Finnish (FIN)

AF:

0.261

AC:

13297

AN:

50914

Middle Eastern (MID)

AF:

0.280

AC:

1560

AN:

5580

European-Non Finnish (NFE)

AF:

0.236

AC:

249310

AN:

1054972

Other (OTH)

AF:

0.236

AC:

13551

AN:

57328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13156

26311

39467

52622

65778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8566

17132

25698

34264

42830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33476

AN:

152112

Hom.:

3883

Cov.:

AF XY:

0.219

AC XY:

16295

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.155

AC:

6432

AN:

41508

American (AMR)

AF:

0.240

AC:

3669

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3466

East Asian (EAS)

AF:

0.309

AC:

1592

AN:

5160

South Asian (SAS)

AF:

0.182

AC:

878

AN:

4816

European-Finnish (FIN)

AF:

0.275

AC:

2913

AN:

10576

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16403

AN:

67980

Other (OTH)

AF:

0.223

AC:

470

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1396

2791

4187

5582

6978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.237

Hom.:

5559

Bravo

AF:

0.220

Asia WGS

AF:

0.207

AC:

719

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.25

(source)

DANN

Benign

0.50

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over