rs3840006

Variant names:

• chr14-104711014-CA-C
• rs3840006
• NM_022489.4:c.2310+8delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_022489.4(INF2):​c.2310+8delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27179 hom., cov: 0)
  • Exomes 𝑓: 0.56 (234135 hom.)
• Consequence: INF2 NM_022489.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.665
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease dominant intermediate E

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• focal segmental glomerulosclerosis 5

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-104711014-CA-C is Benign according to our data. Variant chr14-104711014-CA-C is described in ClinVar as Benign. ClinVar VariationId is 261606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	NM_022489.4	MANE Select	c.2310+8delA		splice_region intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.2310+8delA		splice_region intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.2310+8delA		splice_region intron	N/A	NP_001413792.1	Q27J81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	ENST00000392634.9	TSL:5 MANE Select	c.2310+8delA		splice_region intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.2310+8delA		splice_region intron	N/A	ENSP00000483829.2	A0A087X118
	INF2	ENST00000675207.1		c.2406+8delA		splice_region intron	N/A	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90046 AN: 151950 Hom.: 27158 Cov.: 0

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.620

GnomAD2 exomes AF: 0.607 AC: 148676 AN: 244882 AF XY: 0.599

Gnomad AFR exome AF: 0.640

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.920

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.562 AC: 819702 AN: 1459118 Hom.: 234135 Cov.: 0 AF XY: 0.562 AC XY: 407783 AN XY: 725784

African (AFR) AF: 0.639 AC: 21382 AN: 33440

American (AMR) AF: 0.695 AC: 30997 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14942 AN: 26118

East Asian (EAS) AF: 0.908 AC: 35967 AN: 39616

South Asian (SAS) AF: 0.616 AC: 53065 AN: 86156

European-Finnish (FIN) AF: 0.529 AC: 27515 AN: 52022

Middle Eastern (MID) AF: 0.589 AC: 3392 AN: 5762

European-Non Finnish (NFE) AF: 0.538 AC: 597699 AN: 1111106

Other (OTH) AF: 0.576 AC: 34743 AN: 60304

GnomAD4 genome AF: 0.593 AC: 90110 AN: 152068 Hom.: 27179 Cov.: 0 AF XY: 0.597 AC XY: 44337 AN XY: 74324

African (AFR) AF: 0.641 AC: 26587 AN: 41458

American (AMR) AF: 0.653 AC: 9989 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3468

East Asian (EAS) AF: 0.914 AC: 4725 AN: 5168

South Asian (SAS) AF: 0.625 AC: 3018 AN: 4830

European-Finnish (FIN) AF: 0.537 AC: 5687 AN: 10588

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36168 AN: 67950

Other (OTH) AF: 0.621 AC: 1310 AN: 2110

Alfa AF: 0.440 Hom.: 2216

Bravo AF: 0.606

Asia WGS AF: 0.779 AC: 2705 AN: 3478

EpiCase AF: 0.531

EpiControl AF: 0.540

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	1	Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	Focal segmental glomerulosclerosis (1)
-	-	1	Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3840006;

hg19: chr14-105177351;

COSMIC: COSV53031816;

COSMIC: COSV53031816;