11-299411-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001025295.3(IFITM5):c.80G>C(p.Gly27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,556,868 control chromosomes in the GnomAD database, including 112,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 17310 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94821 hom. )

Consequence

IFITM5
NM_001025295.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.104

Publications

21 publications found

Variant links:

Genes affected

IFITM5 (HGNC:16644): (interferon induced transmembrane protein 5) This gene encodes a membrane protein thought to play a role in bone mineralization. This gene is located on chromosome 11 in a cluster of related genes which are induced by interferon, however, this gene has not been shown to be interferon inducible. A similar gene, located in a gene cluster on mouse chromosome 7, is a member of the interferon-inducible fragilis gene family. The mouse gene encodes a transmembrane protein described as participating in germ cell competence. A mutation in the 5' UTR of this gene has been associated with osteogenesis imperfecta type V (PMID: 22863190, 22863195). [provided by RefSeq, Aug 2012]

IFITM5 Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 5
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

IFITM5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.3203142E-6).

BP6

Variant 11-299411-C-G is Benign according to our data. Variant chr11-299411-C-G is described in ClinVar as Benign. ClinVar VariationId is 193131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025295.3. 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
	IFITM5	NM_001025295.3	MANE Select	c.80G>C	p.Gly27Ala	missense	Exon 1 of 2	NP_001020466.1	A6NNB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM5	ENST00000382614.2	TSL:1 MANE Select	c.80G>C	p.Gly27Ala	missense	Exon 1 of 2	ENSP00000372059.2	A6NNB3

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68267

AN:

151904

Hom.:

17267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.431

GnomAD2 exomes

AF:

0.451

AC:

76453

AN:

169550

AF XY:

0.444

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.351

AC:

493297

AN:

1404846

Hom.:

94821

Cov.:

AF XY:

0.356

AC XY:

247238

AN XY:

695098

show subpopulations

African (AFR)

AF:

0.672

AC:

21043

AN:

31316

American (AMR)

AF:

0.611

AC:

22175

AN:

36292

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8473

AN:

24290

East Asian (EAS)

AF:

0.660

AC:

24067

AN:

36442

South Asian (SAS)

AF:

0.563

AC:

44507

AN:

79040

European-Finnish (FIN)

AF:

0.353

AC:

17382

AN:

49176

Middle Eastern (MID)

AF:

0.416

AC:

2327

AN:

5596

European-Non Finnish (NFE)

AF:

0.305

AC:

331143

AN:

1084590

Other (OTH)

AF:

0.382

AC:

22180

AN:

58104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15522

31044

46567

62089

77611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11472

22944

34416

45888

57360

<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:

0.450

AC:

68359

AN:

152022

Hom.:

17310

Cov.:

AF XY:

0.458

AC XY:

33987

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.653

AC:

27088

AN:

41466

American (AMR)

AF:

0.534

AC:

8158

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.651

AC:

3352

AN:

5148

South Asian (SAS)

AF:

0.587

AC:

2828

AN:

4820

European-Finnish (FIN)

AF:

0.360

AC:

3806

AN:

10582

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20698

AN:

67936

Other (OTH)

AF:

0.436

AC:

921

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1779

3558

5336

7115

8894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.166

Hom.:

1013

Bravo

AF:

0.472

ESP6500AA

AF:

0.598

AC:

2610

ESP6500EA

AF:

0.281

AC:

2407

ExAC

AF:

0.387

AC:

44760

Asia WGS

AF:

0.648

AC:

2252

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis imperfecta type 5 (4)

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.9

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.030

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0000063

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

PhyloP100

-0.10

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.69

Polyphen

0.0060

Vest4

0.060

MPC

0.014

ClinPred

0.0084

GERP RS

2.3

PromoterAI

-0.0096

Neutral

(source)

Varity_R

0.045

gMVP

0.53

Mutation Taster

=76/24

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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