rs11850821

Positions:

• chr14-104708748-A-G

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.1949+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,970 control chromosomes in the GnomAD database, including 16,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (5755 hom., cov: 33)
  • Exomes 𝑓: 0.098 (10982 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.77

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=-0.79).
• BP6: Variant 14-104708748-A-G is Benign according to our data. Variant chr14-104708748-A-G is described in ClinVar as [Benign]. Clinvar id is 261605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104708748-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.1949+16A>G		intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.1949+16A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.1949+16A>G		intron_variant		5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30819 AN: 152048 Hom.: 5735 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.107 AC: 26632 AN: 248692 Hom.: 2944 AF XY: 0.103 AC XY: 13920 AN XY: 135158

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.0720

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0140

Gnomad SAS exome AF: 0.0849

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0937

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0984 AC: 143589 AN: 1459804 Hom.: 10982 Cov.: 33 AF XY: 0.0979 AC XY: 71086 AN XY: 726244

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.0795

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.0850

Gnomad4 FIN exome AF: 0.0528

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.203 AC: 30885 AN: 152166 Hom.: 5755 Cov.: 33 AF XY: 0.196 AC XY: 14572 AN XY: 74390

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.189

Alfa AF: 0.141 Hom.: 882

Bravo AF: 0.220

Asia WGS AF: 0.0910 AC: 317 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	PreventionGenetics, part of Exact Sciences	-	- -
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, 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	-0.79
CADD	Benign	0.011
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs11850821; hg19: chr14-105175085; COSMIC: COSV53031028; COSMIC: COSV53031028;