chr14-104706192-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022489.4(INF2):c.843+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,555,734 control chromosomes in the GnomAD database, including 4,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 333 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4584 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.14

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-104706192-C-T is Benign according to our data. Variant chr14-104706192-C-T is described in ClinVar as Benign. ClinVar VariationId is 261628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.843+16C>T		intron_variant	Intron 6 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.843+16C>T		intron_variant	Intron 6 of 22	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8994

AN:

152160

Hom.:

333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0604

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0795

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0840

Gnomad OTH

AF:

0.0683

GnomAD2 exomes

AF:

0.0685

AC:

11421

AN:

166610

AF XY:

0.0719

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.0443

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.0148

Gnomad FIN exome

AF:

0.0531

Gnomad NFE exome

AF:

0.0862

Gnomad OTH exome

AF:

0.0963

GnomAD4 exome

AF:

0.0765

AC:

107317

AN:

1403456

Hom.:

4584

Cov.:

AF XY:

0.0778

AC XY:

53853

AN XY:

692062

show subpopulations

African (AFR)

AF:

0.0156

AC:

502

AN:

32092

American (AMR)

AF:

0.0475

AC:

1743

AN:

36730

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2578

AN:

25136

East Asian (EAS)

AF:

0.0104

AC:

381

AN:

36486

South Asian (SAS)

AF:

0.0817

AC:

6531

AN:

79926

European-Finnish (FIN)

AF:

0.0513

AC:

2503

AN:

48830

Middle Eastern (MID)

AF:

0.103

AC:

512

AN:

4970

European-Non Finnish (NFE)

AF:

0.0814

AC:

87971

AN:

1081168

Other (OTH)

AF:

0.0791

AC:

4596

AN:

58118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5022

10044

15067

20089

25111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3218

6436

9654

12872

16090

<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:

0.0590

AC:

8991

AN:

152278

Hom.:

333

Cov.:

AF XY:

0.0573

AC XY:

4270

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0197

AC:

819

AN:

41568

American (AMR)

AF:

0.0602

AC:

922

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

378

AN:

3472

East Asian (EAS)

AF:

0.0101

AC:

AN:

5174

South Asian (SAS)

AF:

0.0795

AC:

384

AN:

4828

European-Finnish (FIN)

AF:

0.0466

AC:

495

AN:

10622

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0839

AC:

5706

AN:

67982

Other (OTH)

AF:

0.0699

AC:

148

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

444

888

1331

1775

2219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0780

Hom.:

Bravo

AF:

0.0569

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Dec 29, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.50

PhyloP100

-1.1

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

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