rs59751492

Positions:

chr14-104711090-C-T

Variant summary

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

The NM_022489.4(INF2):c.2322C>T(p.Thr774Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,598,020 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 120 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 116 hom. )

Consequence

INF2
NM_022489.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -9.08

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=-0.73).

BP6

Variant 14-104711090-C-T is Benign according to our data. Variant chr14-104711090-C-T is described in ClinVar as [Benign]. Clinvar id is 261607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104711090-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-9.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 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.2322C>T	p.Thr774Thr	synonymous_variant	15/23	ENST00000392634.9	NP_071934.3	Q27J81-1
INF2	NM_001031714.4 linkuse as main transcript	c.2322C>T	p.Thr774Thr	synonymous_variant	15/22		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.2322C>T	p.Thr774Thr	synonymous_variant	15/23	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3379

AN:

152168

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0742

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00644

AC:

1408

AN:

218664

Hom.:

AF XY:

0.00539

AC XY:

646

AN XY:

119786

show subpopulations

Gnomad AFR exome

AF:

0.0737

Gnomad AMR exome

AF:

0.00412

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00628

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.000882

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00322

AC:

4651

AN:

1445734

Hom.:

116

Cov.:

AF XY:

0.00309

AC XY:

2219

AN XY:

718332

show subpopulations

Gnomad4 AFR exome

AF:

0.0756

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000789

Gnomad4 SAS exome

AF:

0.00591

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.000605

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.0222

AC:

3383

AN:

152286

Hom.:

120

Cov.:

AF XY:

0.0212

AC XY:

1582

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0741

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0253

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	GeneDx	Jun 28, 2016	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	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 01, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 05, 2019	- -

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

Jan 31, 2024

- -

Kidney disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 01, 2018

- -

Focal segmental glomerulosclerosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.036

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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