11-298516-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001025295.3(IFITM5):c.384C>T(p.Asp128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,611,422 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (15 hom.)
• Consequence: IFITM5 NM_001025295.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.38

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-298516-G-A is Benign according to our data. Variant chr11-298516-G-A is described in ClinVar as [Benign]. Clinvar id is 741824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.38 with no splicing effect.
• BS2: High AC in GnomAd at 252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFITM5	NM_001025295.3	c.384C>T	p.Asp128=	synonymous_variant	2/2	ENST00000382614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFITM5	ENST00000382614.2	c.384C>T	p.Asp128=	synonymous_variant	2/2	1	NM_001025295.3	P1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152198 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00231 AC: 575 AN: 248650 Hom.: 7 AF XY: 0.00210 AC XY: 283 AN XY: 134988

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.0169

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00330

GnomAD4 exome AF: 0.00135 AC: 1967 AN: 1459224 Hom.: 15 Cov.: 31 AF XY: 0.00122 AC XY: 884 AN XY: 725884

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.000839

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00166 AC: 252 AN: 152198 Hom.: 1 Cov.: 33 AF XY: 0.00215 AC XY: 160 AN XY: 74348

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000450

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis imperfecta Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 12, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs144153945; hg19: chr11-298516;