NM_022489.4:c.*536G>T

Variant names:

• chr14-104719329-G-T
• rs1128880
• NM_022489.4:c.*536G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

INF2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease dominant intermediate E

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• focal segmental glomerulosclerosis 5

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 312721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	NM_022489.4	MANE Select	c.*536G>T		3_prime_UTR	Exon 23 of 23	NP_071934.3
	INF2	NM_001426862.1		c.*506G>T		3_prime_UTR	Exon 23 of 23	NP_001413791.1
	INF2	NM_001426863.1		c.*536G>T		3_prime_UTR	Exon 23 of 23	NP_001413792.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	ENST00000392634.9	TSL:5 MANE Select	c.*536G>T		3_prime_UTR	Exon 23 of 23	ENSP00000376410.4
	INF2	ENST00000617571.5	TSL:1	n.*1135G>T		non_coding_transcript_exon	Exon 22 of 22	ENSP00000483829.2
	INF2	ENST00000617571.5	TSL:1	n.*1135G>T		3_prime_UTR	Exon 22 of 22	ENSP00000483829.2

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

African (AFR) AF: 0.125 AC: 3 AN: 24

American (AMR) AF: 0.579 AC: 66 AN: 114

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 22 AN: 44

East Asian (EAS) AF: 0.917 AC: 44 AN: 48

South Asian (SAS) AF: 0.564 AC: 53 AN: 94

European-Finnish (FIN) AF: 0.438 AC: 21 AN: 48

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.519 AC: 667 AN: 1286

Other (OTH) AF: 0.510 AC: 52 AN: 102

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

African (AFR) AF: 0.289 AC: 11969 AN: 41486

American (AMR) AF: 0.588 AC: 8990 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4580 AN: 5148

South Asian (SAS) AF: 0.564 AC: 2713 AN: 4814

European-Finnish (FIN) AF: 0.494 AC: 5220 AN: 10572

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34490 AN: 67910

Other (OTH) AF: 0.518 AC: 1092 AN: 2108

Alfa AF: 0.481 Hom.: 10330

Bravo AF: 0.471

Asia WGS AF: 0.695 AC: 2412 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 5 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.55
DANN	Benign	0.68
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1128880; hg19: chr14-105185666;