14-104701320-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23

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 -14 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_single_submitter, 1 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 GnomAd at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.-9-37C>T		intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.-9-37C>T		intron_variant
INF2	NM_032714.3	c.-9-37C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 152254 Hom.: 1 Cov.: 33

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.: 1 AF XY: 0.00214 AC XY: 176 AN XY: 82154

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.: 3 Cov.: 31 AF XY: 0.00275 AC XY: 1878 AN XY: 682496

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.: 1 Cov.: 33 AF XY: 0.00243 AC XY: 181 AN XY: 74508

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.: 0

Bravo AF: 0.00210

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2020

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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

Other links and lift over

dbSNP: rs142345234; hg19: chr14-105167657;