rs4074531

chr14-104701773-G-Achr14-104701773-G-C

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.391+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,478,464 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (69 hom., cov: 34)
  • Exomes 𝑓: 0.012 (636 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.88

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=-0.84).
• BP6: Variant 14-104701773-G-A is Benign according to our data. Variant chr14-104701773-G-A is described in ClinVar as [Benign]. Clinvar id is 261622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104701773-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.391+17G>A		intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.391+17G>A		intron_variant
INF2	NM_032714.3	c.391+17G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.391+17G>A		intron_variant		5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1992 AN: 152234 Hom.: 69 Cov.: 34

Gnomad AFR AF: 0.00219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.0360 AC: 3221 AN: 89562 Hom.: 154 AF XY: 0.0369 AC XY: 1736 AN XY: 47108

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.0678

Gnomad FIN exome AF: 0.00619

Gnomad NFE exome AF: 0.00389

Gnomad OTH exome AF: 0.0252

GnomAD4 exome AF: 0.0119 AC: 15798 AN: 1326114 Hom.: 636 Cov.: 35 AF XY: 0.0132 AC XY: 8536 AN XY: 646704

Gnomad4 AFR exome AF: 0.00208

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.0650

Gnomad4 FIN exome AF: 0.00582

Gnomad4 NFE exome AF: 0.00331

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0131 AC: 2000 AN: 152350 Hom.: 69 Cov.: 34 AF XY: 0.0158 AC XY: 1174 AN XY: 74490

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0704

Gnomad4 FIN AF: 0.00602

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00408 Hom.: 2

Bravo AF: 0.0147

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 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	Eurofins Ntd Llc (ga)	Sep 06, 2016	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4074531; hg19: chr14-105168110;