14-104697195-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4	c.-9-4162C>T		intron_variant	Intron 1 of 22	ENST00000392634.9	NP_071934.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9	c.-9-4162C>T		intron_variant	Intron 1 of 22	5	NM_022489.4	ENSP00000376410.4

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.326

Alfa AF: 0.216 Hom.: 5484

Bravo AF: 0.364

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7140154; hg19: chr14-105163532;