rs3840006

chr14-104711014-CA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_022489.4(INF2):c.2310+8del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27179 hom., cov: 0)
  • Exomes 𝑓: 0.56 (234135 hom.)
• Consequence: INF2 NM_022489.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.665

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 -16 ACMG points.

• BP6: Variant 14-104711014-CA-C is Benign according to our data. Variant chr14-104711014-CA-C is described in ClinVar as [Benign]. Clinvar id is 261606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104711014-CA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.2310+8del		splice_region_variant, intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.2310+8del		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.2310+8del		splice_region_variant, intron_variant		5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90046 AN: 151950 Hom.: 27158 Cov.: 0

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.607 AC: 148676 AN: 244882 Hom.: 46562 AF XY: 0.599 AC XY: 80076 AN XY: 133690

Gnomad AFR exome AF: 0.640

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.920

Gnomad SAS exome AF: 0.618

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.562 AC: 819702 AN: 1459118 Hom.: 234135 Cov.: 0 AF XY: 0.562 AC XY: 407783 AN XY: 725784

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.908

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.593 AC: 90110 AN: 152068 Hom.: 27179 Cov.: 0 AF XY: 0.597 AC XY: 44337 AN XY: 74324

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.621

Alfa AF: 0.440 Hom.: 2216

Bravo AF: 0.606

Asia WGS AF: 0.779 AC: 2705 AN: 3478

EpiCase AF: 0.531

EpiControl AF: 0.540

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 18, 2021	- -

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

- -

Charcot-Marie-Tooth disease dominant intermediate E Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 12, 2018

- -

Focal segmental glomerulosclerosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3840006; hg19: chr14-105177351; COSMIC: COSV53031816; COSMIC: COSV53031816;