rs148541427

Positions:

chr14-104713565-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022489.4(INF2):c.2999G>A(p.Ser1000Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,612,422 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

INF2
NM_022489.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.18

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=0.005710304).

BP6

Variant 14-104713565-G-A is Benign according to our data. Variant chr14-104713565-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00197 (300/152296) while in subpopulation AFR AF= 0.00623 (259/41554). AF 95% confidence interval is 0.00561. There are 4 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4 linkuse as main transcript	c.2999G>A	p.Ser1000Asn	missense_variant	20/23	ENST00000392634.9
INF2	NM_001031714.4 linkuse as main transcript	c.2999G>A	p.Ser1000Asn	missense_variant	20/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.2999G>A	p.Ser1000Asn	missense_variant	20/23	5	NM_022489.4	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

295

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000707

AC:

174

AN:

246242

Hom.:

AF XY:

0.000566

AC XY:

AN XY:

134224

show subpopulations

Gnomad AFR exome

AF:

0.00674

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.000278

AC:

406

AN:

1460126

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.00601

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000819

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

152296

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000493

Hom.:

Bravo

AF:

0.00249

ESP6500AA

AF:

0.00661

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000729

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 21, 2024

- -

Kidney disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.046

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.093

Sift

Benign

0.40

T;T;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.086

MVP

0.19

MPC

0.23

ClinPred

0.00082

GERP RS

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.15

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