rs12252

Variant names:

• chr11-320772-A-G
• rs12252
• NM_021034.3:c.42T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021034.3(IFITM3):​c.42T>C​(p.Ser14Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 1,613,456 control chromosomes in the GnomAD database, including 13,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (2447 hom., cov: 33)
  • Exomes 𝑓: 0.070 (11000 hom.)
• Consequence: IFITM3 NM_021034.3 synonymous
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -5.37
• Publications: 283 publications found

Genes affected

IFITM3 (HGNC:5414): (interferon induced transmembrane protein 3) Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]

IFITM3-AS1 (HGNC:58185):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021034.3. 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
	IFITM3	NM_021034.3	MANE Select	c.42T>C	p.Ser14Ser	synonymous	Exon 1 of 2	NP_066362.2	Q01628
	IFITM3	NR_049759.2		n.89T>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3	ENST00000399808.5	TSL:1 MANE Select	c.42T>C	p.Ser14Ser	synonymous	Exon 1 of 2	ENSP00000382707.4	Q01628
	IFITM3-AS1	ENST00000602429.2	TSL:1	n.115+2026A>G		intron	N/A
	IFITM3	ENST00000526811.4	TSL:5	c.-22T>C		splice_region	Exon 2 of 3	ENSP00000432108.1	E9PS44

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19820 AN: 151944 Hom.: 2447 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.127 AC: 31738 AN: 249316 AF XY: 0.119

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.0994

Gnomad EAS exome AF: 0.560

Gnomad FIN exome AF: 0.0782

Gnomad NFE exome AF: 0.0394

Gnomad OTH exome AF: 0.0893

GnomAD4 exome AF: 0.0704 AC: 102914 AN: 1461394 Hom.: 11000 Cov.: 35 AF XY: 0.0711 AC XY: 51671 AN XY: 727012

African (AFR) AF: 0.261 AC: 8724 AN: 33454

American (AMR) AF: 0.177 AC: 7928 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 2480 AN: 26126

East Asian (EAS) AF: 0.585 AC: 23211 AN: 39696

South Asian (SAS) AF: 0.120 AC: 10338 AN: 86238

European-Finnish (FIN) AF: 0.0747 AC: 3986 AN: 53376

Middle Eastern (MID) AF: 0.0803 AC: 452 AN: 5628

European-Non Finnish (NFE) AF: 0.0358 AC: 39858 AN: 1111806

Other (OTH) AF: 0.0984 AC: 5937 AN: 60358

GnomAD4 genome AF: 0.131 AC: 19853 AN: 152062 Hom.: 2447 Cov.: 33 AF XY: 0.134 AC XY: 9995 AN XY: 74364

African (AFR) AF: 0.250 AC: 10347 AN: 41448

American (AMR) AF: 0.124 AC: 1898 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2845 AN: 5166

South Asian (SAS) AF: 0.135 AC: 652 AN: 4822

European-Finnish (FIN) AF: 0.0780 AC: 827 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0388 AC: 2634 AN: 67956

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.0744 Hom.: 391

Bravo AF: 0.146

Asia WGS AF: 0.299 AC: 1037 AN: 3478

EpiCase AF: 0.0412

EpiControl AF: 0.0404

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Influenza, severe, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		-5.4
PromoterAI		0.086	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
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: rs12252; hg19: chr11-320772; COSMIC: COSV67707031; COSMIC: COSV67707031;