Variant rs4074531 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.391+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,478,464 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 69 hom., cov: 34)

Exomes 𝑓: 0.012 ( 636 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.88

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=-0.84).

BP6

Variant 14-104701773-G-A is Benign according to our data. Variant chr14-104701773-G-A is described in ClinVar as [Benign]. Clinvar id is 261622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104701773-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
INF2	NM_022489.4 linkuse as main transcript	c.391+17G>A	intron_variant	ENST00000392634.9	NP_071934.3
INF2	NM_001031714.4 linkuse as main transcript	c.391+17G>A	intron_variant		NP_001026884.3
INF2	NM_032714.3 linkuse as main transcript	c.391+17G>A	intron_variant		NP_116103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.391+17G>A		intron_variant		5	NM_022489.4	ENSP00000376410	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1992

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0705

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0360

AC:

3221

AN:

89562

Hom.:

154

AF XY:

0.0369

AC XY:

1736

AN XY:

47108

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.0678

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.0252

GnomAD4 exome

AF:

0.0119

AC:

15798

AN:

1326114

Hom.:

636

Cov.:

AF XY:

0.0132

AC XY:

8536

AN XY:

646704

show subpopulations

Gnomad4 AFR exome

AF:

0.00208

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.0650

Gnomad4 FIN exome

AF:

0.00582

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.0210

GnomAD4 genome

AF:

0.0131

AC:

2000

AN:

152350

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1174

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.0333

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.0704

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 06, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 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. -

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

- -

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

-0.84

CADD

Benign

2.1

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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