chr14-104719329-G-T

Variant names:

• chr14-104719329-G-T
• rs1128880
• NM_022489.4:c.*536G>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.*536G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 153,774 control chromosomes in the GnomAD database, including 18,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18293 hom., cov: 33)
  • Exomes 𝑓: 0.53 (255 hom.)
• Consequence: INF2 NM_022489.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.92

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=-0.95).
• BP6: Variant 14-104719329-G-T is Benign according to our data. Variant chr14-104719329-G-T is described in ClinVar as [Benign]. Clinvar id is 312721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104719329-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4	c.*536G>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000392634.9	NP_071934.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9	c.*536G>T		3_prime_UTR_variant	Exon 23 of 23	5	NM_022489.4	ENSP00000376410.4

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71495 AN: 151892 Hom.: 18290 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.527 AC: 930 AN: 1764 Hom.: 255 Cov.: 0 AF XY: 0.509 AC XY: 466 AN XY: 916

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.579

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.917

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.470 AC: 71520 AN: 152010 Hom.: 18293 Cov.: 33 AF XY: 0.476 AC XY: 35348 AN XY: 74300

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.518

Alfa AF: 0.477 Hom.: 8670

Bravo AF: 0.471

Asia WGS AF: 0.695 AC: 2412 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 83. Only high quality variants are reported. -

Focal segmental glomerulosclerosis 5 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.55
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1128880; hg19: chr14-105185666;