dbSNP rs2071242: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLII	NM_002018.4 link	c.1596+69A>G		intron_variant	Intron 13 of 29	ENST00000327031.9	NP_002009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLII	ENST00000327031.9 link	c.1596+69A>G		intron_variant	Intron 13 of 29	1	NM_002018.4	ENSP00000324573.4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over