Variant chr14-104689664-G-A 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.-85G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 982,220 control chromosomes in the GnomAD database, including 7,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 885 hom., cov: 31)

Exomes 𝑓: 0.13 ( 6994 hom. )

Consequence

INF2
NM_022489.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.148

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=-0.77).

BP6

Variant 14-104689664-G-A is Benign according to our data. Variant chr14-104689664-G-A is described in ClinVar as [Benign]. Clinvar id is 312673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104689664-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
INF2	NM_022489.4 linkuse as main transcript	c.-85G>A	5_prime_UTR_variant	1/23	ENST00000392634.9
INF2	NM_001031714.4 linkuse as main transcript	c.-85G>A	5_prime_UTR_variant	1/22
INF2	NM_032714.3 linkuse as main transcript	c.-85G>A	5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.-85G>A		5_prime_UTR_variant	1/23	5	NM_022489.4	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0930

AC:

13994

AN:

150434

Hom.:

884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0871

Gnomad EAS

AF:

0.0546

Gnomad SAS

AF:

0.0888

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0952

GnomAD4 exome

AF:

0.129

AC:

107130

AN:

831682

Hom.:

6994

Cov.:

AF XY:

0.129

AC XY:

49532

AN XY:

384086

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0662

Gnomad4 ASJ exome

AF:

0.0875

Gnomad4 EAS exome

AF:

0.0394

Gnomad4 SAS exome

AF:

0.0826

Gnomad4 FIN exome

AF:

0.0912

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0930

AC:

13995

AN:

150538

Hom.:

885

Cov.:

AF XY:

0.0927

AC XY:

6820

AN XY:

73566

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.0908

Gnomad4 ASJ

AF:

0.0871

Gnomad4 EAS

AF:

0.0548

Gnomad4 SAS

AF:

0.0895

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.106

Hom.:

136

Bravo

AF:

0.0877

Asia WGS

AF:

0.0580

AC:

199

AN:

3424

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 16, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Focal segmental glomerulosclerosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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