Variant rs11850821 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 (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 id is 261605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104708748-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
INF2	NM_022489.4 linkuse as main transcript	c.1949+16A>G		intron_variant		ENST00000392634.9
INF2	NM_001031714.4 linkuse as main transcript	c.1949+16A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.1949+16A>G		intron_variant		5	NM_022489.4	P4	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

GnomAD3 exomes

AF:

0.107

AC:

26632

AN:

248692

Hom.:

2944

AF XY:

0.103

AC XY:

13920

AN XY:

135158

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 SAS exome

AF:

0.0849

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

Gnomad4 AFR exome

AF:

0.520

Gnomad4 AMR exome

AF:

0.0795

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.0850

Gnomad4 FIN exome

AF:

0.0528

Gnomad4 NFE exome

AF:

0.0909

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.203

AC:

30885

AN:

152166

Hom.:

5755

Cov.:

AF XY:

0.196

AC XY:

14572

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0848

Gnomad4 FIN

AF:

0.0477

Gnomad4 NFE

AF:

0.0950

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.141

Hom.:

882

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

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

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

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.011

DANN

Benign

0.67

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