Variant chr14-104701320-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022489.4(INF2):c.-9-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,539,958 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 3 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.23

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-104701320-C-T is Benign according to our data. Variant chr14-104701320-C-T is described in ClinVar as [Benign]. Clinvar id is 1234542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00253 (386/152372) while in subpopulation NFE AF= 0.00388 (264/68028). AF 95% confidence interval is 0.0035. There are 1 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
INF2	NM_022489.4 linkuse as main transcript	c.-9-37C>T	intron_variant	ENST00000392634.9
INF2	NM_001031714.4 linkuse as main transcript	c.-9-37C>T	intron_variant
INF2	NM_032714.3 linkuse as main transcript	c.-9-37C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.-9-37C>T		intron_variant		5	NM_022489.4	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000747

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00207

AC:

314

AN:

151680

Hom.:

AF XY:

0.00214

AC XY:

176

AN XY:

82154

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000747

Gnomad ASJ exome

AF:

0.000239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.00438

Gnomad NFE exome

AF:

0.00333

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.00274

AC:

3804

AN:

1387586

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

1878

AN XY:

682496

show subpopulations

Gnomad4 AFR exome

AF:

0.000571

Gnomad4 AMR exome

AF:

0.000907

Gnomad4 ASJ exome

AF:

0.000519

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00459

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152372

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00301

Hom.:

Bravo

AF:

0.00210

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.21

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over