14-104701773-G-A

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.391+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,478,464 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 69 hom., cov: 34)

Exomes 𝑓: 0.012 ( 636 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.88

Publications

2 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=-0.84).

BP6

Variant 14-104701773-G-A is Benign according to our data. Variant chr14-104701773-G-A is described in ClinVar as Benign. ClinVar VariationId is 261622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.391+17G>A		intron_variant	Intron 2 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.391+17G>A		intron_variant	Intron 2 of 22	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1992

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0705

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.0360

AC:

3221

AN:

89562

AF XY:

0.0369

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.0252

GnomAD4 exome

AF:

0.0119

AC:

15798

AN:

1326114

Hom.:

636

Cov.:

AF XY:

0.0132

AC XY:

8536

AN XY:

646704

show subpopulations

African (AFR)

AF:

0.00208

AC:

AN:

29840

American (AMR)

AF:

0.0520

AC:

1426

AN:

27404

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

240

AN:

21172

East Asian (EAS)

AF:

0.133

AC:

4701

AN:

35442

South Asian (SAS)

AF:

0.0650

AC:

4467

AN:

68684

European-Finnish (FIN)

AF:

0.00582

AC:

211

AN:

36266

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.00331

AC:

3463

AN:

1046900

Other (OTH)

AF:

0.0210

AC:

1159

AN:

55080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

836

1673

2509

3346

4182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.0131

AC:

2000

AN:

152350

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1174

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

41588

American (AMR)

AF:

0.0333

AC:

510

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

664

AN:

5174

South Asian (SAS)

AF:

0.0704

AC:

340

AN:

4830

European-Finnish (FIN)

AF:

0.00602

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00363

AC:

247

AN:

68026

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00409

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Sep 06, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2016

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 02, 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

-0.84

CADD

Benign

2.1

(source)

DANN

Benign

0.71

PhyloP100

-2.9

PromoterAI

-0.065

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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