14-104689664-G-A

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.-85G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 982,220 control chromosomes in the GnomAD database, including 7,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (885 hom., cov: 31)
  • Exomes 𝑓: 0.13 (6994 hom.)
• Consequence: INF2 NM_022489.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148

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=-0.77).
• BP6: Variant 14-104689664-G-A is Benign according to our data. Variant chr14-104689664-G-A is described in ClinVar as [Benign]. Clinvar id is 312673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104689664-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.-85G>A		5_prime_UTR_variant	1/23	ENST00000392634.9
INF2	NM_001031714.4	c.-85G>A		5_prime_UTR_variant	1/22
INF2	NM_032714.3	c.-85G>A		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.-85G>A		5_prime_UTR_variant	1/23	5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 13994 AN: 150434 Hom.: 884 Cov.: 31

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0952

GnomAD4 exome AF: 0.129 AC: 107130 AN: 831682 Hom.: 6994 Cov.: 27 AF XY: 0.129 AC XY: 49532 AN XY: 384086

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.0662

Gnomad4 ASJ exome AF: 0.0875

Gnomad4 EAS exome AF: 0.0394

Gnomad4 SAS exome AF: 0.0826

Gnomad4 FIN exome AF: 0.0912

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.0930 AC: 13995 AN: 150538 Hom.: 885 Cov.: 31 AF XY: 0.0927 AC XY: 6820 AN XY: 73566

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.0548

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.106 Hom.: 136

Bravo AF: 0.0877

Asia WGS AF: 0.0580 AC: 199 AN: 3424

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Focal segmental glomerulosclerosis 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs141884370; hg19: chr14-105156001;