rs748529803

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_022489.4(INF2):​c.2659G>A​(p.Glu887Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000583 in 1,612,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

INF2
NM_022489.4 missense

Scores

7
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29073113).
BP6
Variant 14-104712876-G-A is Benign according to our data. Variant chr14-104712876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472845.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000596 (87/1460302) while in subpopulation NFE AF= 0.0000702 (78/1111764). AF 95% confidence interval is 0.0000571. There are 0 homozygotes in gnomad4_exome. There are 49 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INF2NM_022489.4 linkuse as main transcriptc.2659G>A p.Glu887Lys missense_variant 18/23 ENST00000392634.9 NP_071934.3
INF2NM_001031714.4 linkuse as main transcriptc.2659G>A p.Glu887Lys missense_variant 18/22 NP_001026884.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INF2ENST00000392634.9 linkuse as main transcriptc.2659G>A p.Glu887Lys missense_variant 18/235 NM_022489.4 ENSP00000376410 P4Q27J81-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000283
AC:
7
AN:
247346
Hom.:
0
AF XY:
0.0000371
AC XY:
5
AN XY:
134854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000870
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:
0.0000359
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000596
AC:
87
AN:
1460302
Hom.:
0
Cov.:
36
AF XY:
0.0000675
AC XY:
49
AN XY:
726452
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
.;T;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-3.2
D;D;.
REVEL
Benign
0.19
Sift
Benign
0.039
D;T;.
Sift4G
Benign
0.43
T;T;T
Polyphen
0.99
D;D;.
Vest4
0.58
MVP
0.24
MPC
0.28
ClinPred
0.66
D
GERP RS
4.9
Varity_R
0.19
gMVP
0.52

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.

Other links and lift over

dbSNP: rs748529803; hg19: chr14-105179213; COSMIC: COSV105869497; COSMIC: COSV105869497; API