14-104689843-G-A

Position:

• chr14-104689843-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022489.4(INF2):​c.-10+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 694,874 control chromosomes in the GnomAD database, including 744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (266 hom., cov: 32)
  • Exomes 𝑓: 0.041 (478 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

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=-0.79).
• BP6: Variant 14-104689843-G-A is Benign according to our data. Variant chr14-104689843-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1254136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.-10+104G>A		intron_variant		ENST00000392634.9
INF2	NM_001031714.4	c.-10+104G>A		intron_variant
INF2	NM_032714.3	c.-10+104G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.-10+104G>A		intron_variant		5	NM_022489.4	P4

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6199 AN: 151872 Hom.: 267 Cov.: 32

Gnomad AFR AF: 0.00961

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0426

GnomAD4 exome AF: 0.0406 AC: 22048 AN: 542894 Hom.: 478 AF XY: 0.0405 AC XY: 10301 AN XY: 254340

Gnomad4 AFR exome AF: 0.00551

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0859

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0911

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0392

Gnomad4 OTH exome AF: 0.0494

GnomAD4 genome AF: 0.0408 AC: 6203 AN: 151980 Hom.: 266 Cov.: 32 AF XY: 0.0431 AC XY: 3198 AN XY: 74280

Gnomad4 AFR AF: 0.00959

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.0992

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0344 Hom.: 17

Bravo AF: 0.0479

Asia WGS AF: 0.0900 AC: 310 AN: 3450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3861679; hg19: chr14-105156180;