rs3840006

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022489.4(INF2):c.2310+8delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27179 hom., cov: 0)

Exomes 𝑓: 0.56 ( 234135 hom. )

Consequence

INF2
NM_022489.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.665

Publications

7 publications found

Variant links:

Genes affected

INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

INF2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease dominant intermediate E
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
focal segmental glomerulosclerosis 5
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

INF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-104711014-CA-C is Benign according to our data. Variant chr14-104711014-CA-C is described in ClinVar as Benign. ClinVar VariationId is 261606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.2310+8delA		splice_region_variant, intron_variant	Intron 14 of 22	ENST00000392634.9	NP_071934.3	Q27J81-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 link	c.2310+8delA		splice_region_variant, intron_variant	Intron 14 of 22	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90046

AN:

151950

Hom.:

27158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.620

GnomAD2 exomes

AF:

0.607

AC:

148676

AN:

244882

AF XY:

0.599

show subpopulations

Gnomad AFR exome

AF:

0.640

Gnomad AMR exome

AF:

0.704

Gnomad ASJ exome

AF:

0.570

Gnomad EAS exome

AF:

0.920

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.562

AC:

819702

AN:

1459118

Hom.:

234135

Cov.:

AF XY:

0.562

AC XY:

407783

AN XY:

725784

show subpopulations

African (AFR)

AF:

0.639

AC:

21382

AN:

33440

American (AMR)

AF:

0.695

AC:

30997

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

14942

AN:

26118

East Asian (EAS)

AF:

0.908

AC:

35967

AN:

39616

South Asian (SAS)

AF:

0.616

AC:

53065

AN:

86156

European-Finnish (FIN)

AF:

0.529

AC:

27515

AN:

52022

Middle Eastern (MID)

AF:

0.589

AC:

3392

AN:

5762

European-Non Finnish (NFE)

AF:

0.538

AC:

597699

AN:

1111106

Other (OTH)

AF:

0.576

AC:

34743

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18428

36855

55283

73710

92138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17192

34384

51576

68768

85960

<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:

0.593

AC:

90110

AN:

152068

Hom.:

27179

Cov.:

AF XY:

0.597

AC XY:

44337

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.641

AC:

26587

AN:

41458

American (AMR)

AF:

0.653

AC:

9989

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1961

AN:

3468

East Asian (EAS)

AF:

0.914

AC:

4725

AN:

5168

South Asian (SAS)

AF:

0.625

AC:

3018

AN:

4830

European-Finnish (FIN)

AF:

0.537

AC:

5687

AN:

10588

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36168

AN:

67950

Other (OTH)

AF:

0.621

AC:

1310

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1878

3757

5635

7514

9392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.440

Hom.:

2216

Bravo

AF:

0.606

Asia WGS

AF:

0.779

AC:

2705

AN:

3478

EpiCase

AF:

0.531

EpiControl

AF:

0.540

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 18, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 84. Only high quality variants are reported. -

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease dominant intermediate E

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over