dbSNP rs186075307: INF2:p.Leu1036Leu (chr14-104714270-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022489.4(INF2):c.3108T>C(p.Leu1036Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,594,960 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0064 ( 36 hom. )

Consequence

INF2
NM_022489.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -2.32

Publications

3 publications found

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 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

INF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-104714270-T-C is Benign according to our data. Variant chr14-104714270-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00527 (802/152224) while in subpopulation NFE AF = 0.00797 (542/67992). AF 95% confidence interval is 0.00742. There are 6 homozygotes in GnomAd4. There are 391 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 802 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INF2	NM_022489.4	MANE Select	c.3108T>C	p.Leu1036Leu	synonymous	Exon 21 of 23	NP_071934.3	Q27J81-1
INF2	NM_001426862.1		c.3108T>C	p.Leu1036Leu	synonymous	Exon 21 of 23	NP_001413791.1
INF2	NM_001426863.1		c.3108T>C	p.Leu1036Leu	synonymous	Exon 21 of 23	NP_001413792.1	Q27J81-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INF2	ENST00000392634.9	TSL:5 MANE Select	c.3108T>C	p.Leu1036Leu	synonymous	Exon 21 of 23	ENSP00000376410.4	Q27J81-1
INF2	ENST00000617571.5	TSL:1	n.3104T>C		non_coding_transcript_exon	Exon 20 of 22	ENSP00000483829.2	A0A087X118
INF2	ENST00000675207.1		c.3204T>C	p.Leu1068Leu	synonymous	Exon 21 of 23	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

804

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00797

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00484

AC:

1056

AN:

218116

AF XY:

0.00472

show subpopulations

Gnomad AFR exome

AF:

0.000905

Gnomad AMR exome

AF:

0.00441

Gnomad ASJ exome

AF:

0.00695

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00193

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00646

GnomAD4 exome

AF:

0.00643

AC:

9273

AN:

1442736

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

4461

AN XY:

716110

show subpopulations

African (AFR)

AF:

0.00112

AC:

AN:

32974

American (AMR)

AF:

0.00509

AC:

218

AN:

42858

Ashkenazi Jewish (ASJ)

AF:

0.00653

AC:

167

AN:

25584

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38728

South Asian (SAS)

AF:

0.000938

AC:

AN:

83154

European-Finnish (FIN)

AF:

0.00247

AC:

123

AN:

49762

Middle Eastern (MID)

AF:

0.00628

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00745

AC:

8227

AN:

1104310

Other (OTH)

AF:

0.00647

AC:

386

AN:

59634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

551

1102

1652

2203

2754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00527

AC:

802

AN:

152224

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41550

American (AMR)

AF:

0.00712

AC:

109

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00797

AC:

542

AN:

67992

Other (OTH)

AF:

0.0109

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00745

Hom.:

Bravo

AF:

0.00591

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (5)

Focal segmental glomerulosclerosis 5 (1)

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.48

(source)

DANN

Benign

0.46

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over