rs118017785

chr14-104706192-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022489.4(INF2):c.843+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,555,734 control chromosomes in the GnomAD database, including 4,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (333 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4584 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.14

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-104706192-C-T is Benign according to our data. Variant chr14-104706192-C-T is described in ClinVar as [Benign]. Clinvar id is 261628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104706192-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.843+16C>T		intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.843+16C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.843+16C>T		intron_variant		5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8994 AN: 152160 Hom.: 333 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.0683

GnomAD3 exomes AF: 0.0685 AC: 11421 AN: 166610 Hom.: 489 AF XY: 0.0719 AC XY: 6418 AN XY: 89310

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0443

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.0148

Gnomad SAS exome AF: 0.0841

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.0862

Gnomad OTH exome AF: 0.0963

GnomAD4 exome AF: 0.0765 AC: 107317 AN: 1403456 Hom.: 4584 Cov.: 32 AF XY: 0.0778 AC XY: 53853 AN XY: 692062

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.0817

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.0791

GnomAD4 genome AF: 0.0590 AC: 8991 AN: 152278 Hom.: 333 Cov.: 33 AF XY: 0.0573 AC XY: 4270 AN XY: 74470

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0101

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.0699

Alfa AF: 0.0796 Hom.: 86

Bravo AF: 0.0569

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 2015	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	-	- -

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.50
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs118017785; hg19: chr14-105172529;