rs11850821

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.1949+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,970 control chromosomes in the GnomAD database, including 16,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 5755 hom., cov: 33)

Exomes 𝑓: 0.098 ( 10982 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.77

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-104708748-A-G is Benign according to our data. Variant chr14-104708748-A-G is described in ClinVar as Benign. ClinVar VariationId is 261605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.1949+16A>G		intron_variant	Intron 10 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.1949+16A>G		intron_variant	Intron 10 of 22	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30819

AN:

152048

Hom.:

5735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.0857

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0951

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.107

AC:

26632

AN:

248692

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.0720

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.0533

Gnomad NFE exome

AF:

0.0937

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.0984

AC:

143589

AN:

1459804

Hom.:

10982

Cov.:

AF XY:

0.0979

AC XY:

71086

AN XY:

726244

show subpopulations

African (AFR)

AF:

0.520

AC:

17380

AN:

33424

American (AMR)

AF:

0.0795

AC:

3554

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3002

AN:

26126

East Asian (EAS)

AF:

0.0106

AC:

421

AN:

39698

South Asian (SAS)

AF:

0.0850

AC:

7335

AN:

86250

European-Finnish (FIN)

AF:

0.0528

AC:

2766

AN:

52388

Middle Eastern (MID)

AF:

0.158

AC:

911

AN:

5762

European-Non Finnish (NFE)

AF:

0.0909

AC:

100966

AN:

1111130

Other (OTH)

AF:

0.120

AC:

7254

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

6374

12747

19121

25494

31868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3790

7580

11370

15160

18950

<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:

0.203

AC:

30885

AN:

152166

Hom.:

5755

Cov.:

AF XY:

0.196

AC XY:

14572

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.500

AC:

20719

AN:

41474

American (AMR)

AF:

0.118

AC:

1800

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3472

East Asian (EAS)

AF:

0.0102

AC:

AN:

5174

South Asian (SAS)

AF:

0.0848

AC:

409

AN:

4824

European-Finnish (FIN)

AF:

0.0477

AC:

506

AN:

10614

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0950

AC:

6462

AN:

67986

Other (OTH)

AF:

0.189

AC:

400

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1018

2036

3053

4071

5089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.144

Hom.:

1413

Bravo

AF:

0.220

Asia WGS

AF:

0.0910

AC:

317

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

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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

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

-0.79

CADD

Benign

0.011

(source)

DANN

Benign

0.67

PhyloP100

-2.8

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over