rs1128840

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022489.4(INF2):c.3207A>C(p.Pro1069Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,595,520 control chromosomes in the GnomAD database, including 258,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1069P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.59 ( 27290 hom., cov: 33)

Exomes 𝑓: 0.56 ( 231039 hom. )

Consequence

INF2
NM_022489.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.33

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:

INF2 (HGNC:):

INF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 14-104714369-A-C is Benign according to our data. Variant chr14-104714369-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 261617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104714369-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 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.3207A>C	p.Pro1069Pro	synonymous_variant	21/23	ENST00000392634.9	NP_071934.3	Q27J81-1
INF2	NM_001031714.4 linkuse as main transcript	c.3207A>C	p.Pro1069Pro	synonymous_variant	21/22		NP_001026884.3	Q27J81-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.3207A>C	p.Pro1069Pro	synonymous_variant	21/23	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90221

AN:

152008

Hom.:

27272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.621

GnomAD3 exomes

AF:

0.609

AC:

132775

AN:

217994

Hom.:

41761

AF XY:

0.602

AC XY:

71587

AN XY:

118966

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.705

Gnomad ASJ exome

AF:

0.573

Gnomad EAS exome

AF:

0.921

Gnomad SAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.588

GnomAD4 exome

AF:

0.561

AC:

810008

AN:

1443394

Hom.:

231039

Cov.:

AF XY:

0.561

AC XY:

402382

AN XY:

716634

show subpopulations

Gnomad4 AFR exome

AF:

0.641

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.907

Gnomad4 SAS exome

AF:

0.615

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.593

AC:

90283

AN:

152126

Hom.:

27290

Cov.:

AF XY:

0.597

AC XY:

44427

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.914

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.622

Alfa

AF:

0.520

Hom.:

695

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 21, 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	Athena Diagnostics	Mar 18, 2021	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 86. Only high quality variants are reported. -

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

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 20, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Charcot-Marie-Tooth disease dominant intermediate E

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Focal segmental glomerulosclerosis 5

Benign:1

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. -

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

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.29

DANN

Benign

0.42

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