rs118017785

Variant names:

• chr14-104706192-C-T
• rs118017785
• NM_022489.4:c.843+16C>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.843+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,555,734 control chromosomes in the GnomAD database, including 4,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (333 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4584 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.14
• Publications: 5 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• BP6: Variant 14-104706192-C-T is Benign according to our data. Variant chr14-104706192-C-T is described in ClinVar as Benign. ClinVar VariationId is 261628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0821 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	NM_022489.4	MANE Select	c.843+16C>T		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.843+16C>T		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.843+16C>T		intron	N/A	NP_001413792.1	Q27J81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	ENST00000392634.9	TSL:5 MANE Select	c.843+16C>T		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.843+16C>T		intron	N/A	ENSP00000483829.2	A0A087X118
	INF2	ENST00000675207.1		c.939+16C>T		intron	N/A	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8994 AN: 152160 Hom.: 333 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.0683

GnomAD2 exomes AF: 0.0685 AC: 11421 AN: 166610 AF XY: 0.0719

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0443

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.0148

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.0862

Gnomad OTH exome AF: 0.0963

GnomAD4 exome AF: 0.0765 AC: 107317 AN: 1403456 Hom.: 4584 Cov.: 32 AF XY: 0.0778 AC XY: 53853 AN XY: 692062

African (AFR) AF: 0.0156 AC: 502 AN: 32092

American (AMR) AF: 0.0475 AC: 1743 AN: 36730

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2578 AN: 25136

East Asian (EAS) AF: 0.0104 AC: 381 AN: 36486

South Asian (SAS) AF: 0.0817 AC: 6531 AN: 79926

European-Finnish (FIN) AF: 0.0513 AC: 2503 AN: 48830

Middle Eastern (MID) AF: 0.103 AC: 512 AN: 4970

European-Non Finnish (NFE) AF: 0.0814 AC: 87971 AN: 1081168

Other (OTH) AF: 0.0791 AC: 4596 AN: 58118

GnomAD4 genome AF: 0.0590 AC: 8991 AN: 152278 Hom.: 333 Cov.: 33 AF XY: 0.0573 AC XY: 4270 AN XY: 74470

African (AFR) AF: 0.0197 AC: 819 AN: 41568

American (AMR) AF: 0.0602 AC: 922 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3472

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5174

South Asian (SAS) AF: 0.0795 AC: 384 AN: 4828

European-Finnish (FIN) AF: 0.0466 AC: 495 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5706 AN: 67982

Other (OTH) AF: 0.0699 AC: 148 AN: 2116

Alfa AF: 0.0780 Hom.: 86

Bravo AF: 0.0569

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-1.1
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs118017785; hg19: chr14-105172529;