14-104714315-C-T

Position:

chr14-104714315-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022489.4(INF2):c.3153C>T(p.Asp1051=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,589,492 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 30 hom., cov: 34)

Exomes 𝑓: 0.015 ( 266 hom. )

Consequence

INF2
NM_022489.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.34

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 14-104714315-C-T is Benign according to our data. Variant chr14-104714315-C-T is described in ClinVar as [Benign]. Clinvar id is 261616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104714315-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0131 (1993/152122) while in subpopulation SAS AF= 0.0453 (218/4810). AF 95% confidence interval is 0.0404. There are 30 homozygotes in gnomad4. There are 1098 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INF2	NM_022489.4 linkuse as main transcript	c.3153C>T	p.Asp1051=	synonymous_variant	21/23	ENST00000392634.9	NP_071934.3
INF2	NM_001031714.4 linkuse as main transcript	c.3153C>T	p.Asp1051=	synonymous_variant	21/22		NP_001026884.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.3153C>T	p.Asp1051=	synonymous_variant	21/23	5	NM_022489.4	ENSP00000376410	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1998

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0155

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.0426

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0193

AC:

3969

AN:

205650

Hom.:

AF XY:

0.0203

AC XY:

2275

AN XY:

111870

show subpopulations

Gnomad AFR exome

AF:

0.00231

Gnomad AMR exome

AF:

0.00731

Gnomad ASJ exome

AF:

0.00916

Gnomad EAS exome

AF:

0.0204

Gnomad SAS exome

AF:

0.0413

Gnomad FIN exome

AF:

0.0387

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0154

AC:

22092

AN:

1437370

Hom.:

266

Cov.:

AF XY:

0.0160

AC XY:

11407

AN XY:

713118

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00742

Gnomad4 ASJ exome

AF:

0.00991

Gnomad4 EAS exome

AF:

0.0179

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0131

AC:

1993

AN:

152122

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1098

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00239

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.0154

Gnomad4 SAS

AF:

0.0453

Gnomad4 FIN

AF:

0.0426

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00954

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 27, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E

Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 27, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Focal segmental glomerulosclerosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Focal segmental glomerulosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.14

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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