11-298316-C-T

Position:

• chr11-298316-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.*185G>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 0.0908 in 636,776 control chromosomes in the GnomAD database, including 4,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (967 hom., cov: 33)
  • Exomes 𝑓: 0.089 (3036 hom.)
• Consequence: IFITM5 NM_001025295.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.384

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=-0.83).
• BP6: Variant 11-298316-C-T is Benign according to our data. Variant chr11-298316-C-T is described in ClinVar as [Benign]. Clinvar id is 1236321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFITM5	NM_001025295.3	c.*185G>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.*185G>A		3_prime_UTR_variant	2/2	1	NM_001025295.3	P1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14814 AN: 152102 Hom.: 965 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0981

GnomAD4 exome AF: 0.0888 AC: 43011 AN: 484556 Hom.: 3036 Cov.: 5 AF XY: 0.0919 AC XY: 23300 AN XY: 253506

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.0889

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0859

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.0974 AC: 14830 AN: 152220 Hom.: 967 Cov.: 33 AF XY: 0.102 AC XY: 7614 AN XY: 74422

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.0912

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0562 Hom.: 282

Bravo AF: 0.106

Asia WGS AF: 0.202 AC: 702 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 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.64

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: rs2293744; hg19: chr11-298316;