Genetic Variant IFITM5:c.*277G>A (chr11-298224-C-T) – ACMG Classification: Benign (-20 pts)

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.*277G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 480,858 control chromosomes in the GnomAD database, including 756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 290 hom., cov: 33)

Exomes 𝑓: 0.036 ( 466 hom. )

Consequence

IFITM5
NM_001025295.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.645

Publications

3 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

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 (BayesDel_noAF=-0.81).

BP6

Variant 11-298224-C-T is Benign according to our data. Variant chr11-298224-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM5	NM_001025295.3 link	c.*277G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000382614.2	NP_001020466.1	A6NNB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFITM5	ENST00000382614.2 link	c.*277G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001025295.3	ENSP00000372059.2		A6NNB3

Frequencies

GnomAD3 genomes

AF:

0.0502

AC:

7631

AN:

152096

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.0407

Gnomad EAS

AF:

0.0305

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0407

GnomAD4 exome

AF:

0.0358

AC:

11764

AN:

328642

Hom.:

466

Cov.:

AF XY:

0.0412

AC XY:

7048

AN XY:

171164

show subpopulations

African (AFR)

AF:

0.0951

AC:

920

AN:

9674

American (AMR)

AF:

0.0185

AC:

221

AN:

11956

Ashkenazi Jewish (ASJ)

AF:

0.0290

AC:

308

AN:

10616

East Asian (EAS)

AF:

0.0262

AC:

585

AN:

22342

South Asian (SAS)

AF:

0.129

AC:

4264

AN:

32994

European-Finnish (FIN)

AF:

0.0132

AC:

276

AN:

20954

Middle Eastern (MID)

AF:

0.0429

AC:

AN:

1492

European-Non Finnish (NFE)

AF:

0.0222

AC:

4427

AN:

199326

Other (OTH)

AF:

0.0362

AC:

699

AN:

19288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

487

974

1461

1948

2435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.0502

AC:

7638

AN:

152216

Hom.:

290

Cov.:

AF XY:

0.0506

AC XY:

3763

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.103

AC:

4282

AN:

41526

American (AMR)

AF:

0.0308

AC:

472

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

141

AN:

3468

East Asian (EAS)

AF:

0.0304

AC:

157

AN:

5168

South Asian (SAS)

AF:

0.137

AC:

660

AN:

4818

European-Finnish (FIN)

AF:

0.0115

AC:

122

AN:

10608

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0237

AC:

1611

AN:

68008

Other (OTH)

AF:

0.0417

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

359

718

1078

1437

1796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0286

Hom.:

153

Bravo

AF:

0.0505

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.57

(source)

DANN

Benign

0.80

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over