rs59751492

Variant names:

• chr14-104711090-C-T
• rs59751492
• NM_022489.4:c.2322C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-104711090-C-T
• chr14-104711090-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022489.4(INF2):​c.2322C>T​(p.Thr774Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,598,020 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (120 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (116 hom.)
• Consequence: INF2 NM_022489.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -9.08
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-104711090-C-T is Benign according to our data. Variant chr14-104711090-C-T is described in ClinVar as Benign. ClinVar VariationId is 261607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 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.2322C>T	p.Thr774Thr	synonymous	Exon 15 of 23	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.2322C>T	p.Thr774Thr	synonymous	Exon 15 of 23	NP_001413791.1
	INF2	NM_001426863.1		c.2322C>T	p.Thr774Thr	synonymous	Exon 15 of 23	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.2322C>T	p.Thr774Thr	synonymous	Exon 15 of 23	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.2322C>T		non_coding_transcript_exon	Exon 14 of 22	ENSP00000483829.2	A0A087X118
	INF2	ENST00000675207.1		c.2418C>T	p.Thr806Thr	synonymous	Exon 15 of 23	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3379 AN: 152168 Hom.: 121 Cov.: 33

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00644 AC: 1408 AN: 218664 AF XY: 0.00539

Gnomad AFR exome AF: 0.0737

Gnomad AMR exome AF: 0.00412

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000882

Gnomad OTH exome AF: 0.00512

GnomAD4 exome AF: 0.00322 AC: 4651 AN: 1445734 Hom.: 116 Cov.: 34 AF XY: 0.00309 AC XY: 2219 AN XY: 718332

African (AFR) AF: 0.0756 AC: 2469 AN: 32646

American (AMR) AF: 0.00486 AC: 208 AN: 42836

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 261 AN: 25824

East Asian (EAS) AF: 0.0000789 AC: 3 AN: 38028

South Asian (SAS) AF: 0.00591 AC: 497 AN: 84110

European-Finnish (FIN) AF: 0.0000590 AC: 3 AN: 50840

Middle Eastern (MID) AF: 0.0116 AC: 67 AN: 5760

European-Non Finnish (NFE) AF: 0.000605 AC: 669 AN: 1105902

Other (OTH) AF: 0.00793 AC: 474 AN: 59788

GnomAD4 genome AF: 0.0222 AC: 3383 AN: 152286 Hom.: 120 Cov.: 33 AF XY: 0.0212 AC XY: 1582 AN XY: 74464

African (AFR) AF: 0.0741 AC: 3080 AN: 41550

American (AMR) AF: 0.0100 AC: 153 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68012

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0117 Hom.: 16

Bravo AF: 0.0253

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Focal segmental glomerulosclerosis 5 (1)
-	-	1	Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	Kidney disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.036
DANN	Benign	0.90
PhyloP100		-9.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs59751492; hg19: chr14-105177427;