Variant 14-104689755-C-A 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.-10+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 984,884 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 12 hom. )

Consequence

INF2
NM_022489.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.162

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 14-104689755-C-A is Benign according to our data. Variant chr14-104689755-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 380922.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 = 0.00217 (330/152000) while in subpopulation NFE AF= 0.00358 (243/67914). AF 95% confidence interval is 0.00321. There are 0 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 330 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
INF2	NM_022489.4 linkuse as main transcript	c.-10+16C>A	intron_variant	ENST00000392634.9
INF2	NM_001031714.4 linkuse as main transcript	c.-10+16C>A	intron_variant
INF2	NM_032714.3 linkuse as main transcript	c.-10+16C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9 linkuse as main transcript	c.-10+16C>A		intron_variant		5	NM_022489.4	P4	Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00358

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.00374

AC:

3119

AN:

832884

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

1458

AN XY:

384710

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000608

Gnomad4 FIN exome

AF:

0.00355

Gnomad4 NFE exome

AF:

0.00398

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152000

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

164

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00358

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 08, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.9

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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