NM_001025295.3:c.*185G>A

Variant names:

• chr11-298316-C-T
• rs2293744
• NM_001025295.3:c.*185G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.384
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1236321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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.*185G>A		3_prime_UTR	Exon 2 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.*185G>A		3_prime_UTR	Exon 2 of 2	ENSP00000372059.2	A6NNB3

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

African (AFR) AF: 0.128 AC: 1671 AN: 13022

American (AMR) AF: 0.199 AC: 3709 AN: 18620

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 1229 AN: 13830

East Asian (EAS) AF: 0.274 AC: 8515 AN: 31106

South Asian (SAS) AF: 0.147 AC: 6840 AN: 46426

European-Finnish (FIN) AF: 0.0859 AC: 2563 AN: 29832

Middle Eastern (MID) AF: 0.122 AC: 249 AN: 2042

European-Non Finnish (NFE) AF: 0.0519 AC: 15697 AN: 302620

Other (OTH) AF: 0.0938 AC: 2538 AN: 27058

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

African (AFR) AF: 0.128 AC: 5301 AN: 41526

American (AMR) AF: 0.152 AC: 2322 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5156

South Asian (SAS) AF: 0.135 AC: 652 AN: 4828

European-Finnish (FIN) AF: 0.0931 AC: 988 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3553 AN: 68010

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0632 Hom.: 496

Bravo AF: 0.106

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293744; hg19: chr11-298316;