11-298224-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.645

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 -14 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 id is 1286019.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
IFITM5	NM_001025295.3	c.*277G>A		3_prime_UTR_variant	2/2	ENST00000382614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFITM5	ENST00000382614.2	c.*277G>A		3_prime_UTR_variant	2/2	1	NM_001025295.3	P1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7631 AN: 152096 Hom.: 290 Cov.: 33

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.: 0 AF XY: 0.0412 AC XY: 7048 AN XY: 171164

Gnomad4 AFR exome AF: 0.0951

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0290

Gnomad4 EAS exome AF: 0.0262

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.0222

Gnomad4 OTH exome AF: 0.0362

GnomAD4 genome AF: 0.0502 AC: 7638 AN: 152216 Hom.: 290 Cov.: 33 AF XY: 0.0506 AC XY: 3763 AN XY: 74412

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.0407

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0278 Hom.: 45

Bravo AF: 0.0505

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.57
Dann	Benign	0.80

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: rs2293743; hg19: chr11-298224;