rs4074531

Variant names:

• chr14-104701773-G-A
• rs4074531
• NM_022489.4:c.391+17G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104701773-G-A
• chr14-104701773-G-C
• chr14-104701773-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022489.4(INF2):​c.391+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,478,464 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (69 hom., cov: 34)
  • Exomes 𝑓: 0.012 (636 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.88
• Publications: 2 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, ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-104701773-G-A is Benign according to our data. Variant chr14-104701773-G-A is described in ClinVar as Benign. ClinVar VariationId is 261622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 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.391+17G>A		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.391+17G>A		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.391+17G>A		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.391+17G>A		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000398337.8	TSL:1	c.391+17G>A		intron	N/A	ENSP00000381380.4	Q27J81-3
	INF2	ENST00000617571.5	TSL:1	n.391+17G>A		intron	N/A	ENSP00000483829.2	A0A087X118

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1992 AN: 152234 Hom.: 69 Cov.: 34

Gnomad AFR AF: 0.00219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.0360 AC: 3221 AN: 89562 AF XY: 0.0369

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.00619

Gnomad NFE exome AF: 0.00389

Gnomad OTH exome AF: 0.0252

GnomAD4 exome AF: 0.0119 AC: 15798 AN: 1326114 Hom.: 636 Cov.: 35 AF XY: 0.0132 AC XY: 8536 AN XY: 646704

African (AFR) AF: 0.00208 AC: 62 AN: 29840

American (AMR) AF: 0.0520 AC: 1426 AN: 27404

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 240 AN: 21172

East Asian (EAS) AF: 0.133 AC: 4701 AN: 35442

South Asian (SAS) AF: 0.0650 AC: 4467 AN: 68684

European-Finnish (FIN) AF: 0.00582 AC: 211 AN: 36266

Middle Eastern (MID) AF: 0.0130 AC: 69 AN: 5326

European-Non Finnish (NFE) AF: 0.00331 AC: 3463 AN: 1046900

Other (OTH) AF: 0.0210 AC: 1159 AN: 55080

GnomAD4 genome AF: 0.0131 AC: 2000 AN: 152350 Hom.: 69 Cov.: 34 AF XY: 0.0158 AC XY: 1174 AN XY: 74490

African (AFR) AF: 0.00219 AC: 91 AN: 41588

American (AMR) AF: 0.0333 AC: 510 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.128 AC: 664 AN: 5174

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4830

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00363 AC: 247 AN: 68026

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.00409 Hom.: 2

Bravo AF: 0.0147

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-2.9
PromoterAI		-0.065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4074531; hg19: chr14-105168110;