14-104697195-C-T

Variant names:

• chr14-104697195-C-T
• rs7140154
• NM_022489.4:c.-9-4162C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022489.4(INF2):​c.-9-4162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,196 control chromosomes in the GnomAD database, including 11,598 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (11598 hom., cov: 35)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 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.-9-4162C>T		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.-9-4162C>T		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.-9-4162C>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.-9-4162C>T		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000398337.8	TSL:1	c.-9-4162C>T		intron	N/A	ENSP00000381380.4	Q27J81-3
	INF2	ENST00000896057.1		c.-9-4162C>T		intron	N/A	ENSP00000566116.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51382 AN: 152078 Hom.: 11567 Cov.: 35

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51458 AN: 152196 Hom.: 11598 Cov.: 35 AF XY: 0.335 AC XY: 24951 AN XY: 74404

African (AFR) AF: 0.630 AC: 26159 AN: 41526

American (AMR) AF: 0.340 AC: 5198 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2299 AN: 5156

South Asian (SAS) AF: 0.286 AC: 1383 AN: 4830

European-Finnish (FIN) AF: 0.177 AC: 1883 AN: 10620

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12897 AN: 67984

Other (OTH) AF: 0.326 AC: 688 AN: 2110

Alfa AF: 0.226 Hom.: 9274

Bravo AF: 0.364

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.65
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7140154; hg19: chr14-105163532;