dbSNP rs12252: IFITM3:p.Ser14Ser (chr11-320772-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -5.37

Publications

283 publications found

Variant links:

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 links:

ENSG00000251661 (HGNC:58185):

ENSG00000251661 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM3	NM_021034.3 link	c.42T>C	p.Ser14Ser	synonymous_variant	Exon 1 of 2	ENST00000399808.5	NP_066362.2	Q01628

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFITM3	ENST00000399808.5 link	c.42T>C	p.Ser14Ser	synonymous_variant	Exon 1 of 2	1	NM_021034.3	ENSP00000382707.4		Q01628

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19820

AN:

151944

Hom.:

2447

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0711

AC XY:

51671

AN XY:

727012

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4421

8841

13262

17682

22103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2010

4020

6030

8040

10050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.131

AC:

19853

AN:

152062

Hom.:

2447

Cov.:

AF XY:

0.134

AC XY:

9995

AN XY:

74364

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0388

AC:

2634

AN:

67956

Other (OTH)

AF:

0.136

AC:

286

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

772

1544

2315

3087

3859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Influenza, severe, susceptibility to

Other:1

Jan 06, 2014

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.1

(source)

DANN

Benign

0.53

PhyloP100

-5.4

PromoterAI

0.086

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over