rs34251364

Positions:

chr14-104714448-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022489.4(INF2):c.3286C>T(p.Pro1096Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,611,110 control chromosomes in the GnomAD database, including 5,136 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 340 hom., cov: 34)

Exomes 𝑓: 0.077 ( 4796 hom. )

Consequence

INF2
NM_022489.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0460

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017721057).

BP6

Variant 14-104714448-C-T is Benign according to our data. Variant chr14-104714448-C-T is described in ClinVar as [Benign]. Clinvar id is 261619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104714448-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INF2	NM_022489.4 linkuse as main transcript	c.3286C>T	p.Pro1096Ser	missense_variant	21/23	ENST00000392634.9	NP_071934.3
INF2	NM_001031714.4 linkuse as main transcript	c.3286C>T	p.Pro1096Ser	missense_variant	21/22		NP_001026884.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.3286C>T	p.Pro1096Ser	missense_variant	21/23	5	NM_022489.4	ENSP00000376410	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9085

AN:

152162

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.0805

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0842

Gnomad OTH

AF:

0.0669

GnomAD3 exomes

AF:

0.0658

AC:

15891

AN:

241390

Hom.:

650

AF XY:

0.0699

AC XY:

9215

AN XY:

131890

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.0425

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.0140

Gnomad SAS exome

AF:

0.0808

Gnomad FIN exome

AF:

0.0497

Gnomad NFE exome

AF:

0.0825

Gnomad OTH exome

AF:

0.0900

GnomAD4 exome

AF:

0.0767

AC:

111902

AN:

1458830

Hom.:

4796

Cov.:

AF XY:

0.0782

AC XY:

56753

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.0818

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0818

Gnomad4 OTH exome

AF:

0.0791

GnomAD4 genome

AF:

0.0597

AC:

9084

AN:

152280

Hom.:

340

Cov.:

AF XY:

0.0580

AC XY:

4319

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.0600

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.0803

Gnomad4 FIN

AF:

0.0450

Gnomad4 NFE

AF:

0.0842

Gnomad4 OTH

AF:

0.0700

Alfa

AF:

0.0752

Hom.:

243

Bravo

AF:

0.0573

TwinsUK

AF:

0.0809

AC:

300

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.0223

AC:

ESP6500EA

AF:

0.0752

AC:

619

ExAC

AF:

0.0639

AC:

7699

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Focal segmental glomerulosclerosis 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 15, 2017	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.20

.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Benign

0.092

Sift

Uncertain

0.010

D;D;.

Sift4G

Benign

0.17

T;T;T

Polyphen

0.43

B;B;.

Vest4

0.14

MPC

0.25

ClinPred

0.023

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over