Genetic Variant ENSG00000251661:n.115+2242G>A (chr11-320988-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000602429.2(ENSG00000251661):n.115+2242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 145,174 control chromosomes in the GnomAD database, including 15,272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 15272 hom., cov: 32)

Exomes 𝑓: 0.56 ( 83596 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000251661
ENST00000602429.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0830

Publications

11 publications found

Variant links:

Genes affected

ENSG00000251661 (HGNC:58185):

ENSG00000251661 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM3	NM_021034.3 link	c.-175C>T		upstream_gene_variant		ENST00000399808.5	NP_066362.2	Q01628

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFITM3	ENST00000399808.5 link	c.-175C>T		upstream_gene_variant		1	NM_021034.3	ENSP00000382707.4		Q01628

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

73445

AN:

145074

Hom.:

15270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.447

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.489

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.561

AC:

324880

AN:

578690

Hom.:

83596

Cov.:

AF XY:

0.559

AC XY:

168991

AN XY:

302434

show subpopulations

African (AFR)

AF:

0.396

AC:

6289

AN:

15894

American (AMR)

AF:

0.604

AC:

13335

AN:

22072

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

7207

AN:

14418

East Asian (EAS)

AF:

0.620

AC:

18956

AN:

30568

South Asian (SAS)

AF:

0.505

AC:

25318

AN:

50114

European-Finnish (FIN)

AF:

0.634

AC:

19897

AN:

31392

Middle Eastern (MID)

AF:

0.490

AC:

1071

AN:

2186

European-Non Finnish (NFE)

AF:

0.566

AC:

216239

AN:

381974

Other (OTH)

AF:

0.551

AC:

16568

AN:

30072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5876

11752

17627

23503

29379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3018

6036

9054

12072

15090

<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:

0.506

AC:

73485

AN:

145174

Hom.:

15272

Cov.:

AF XY:

0.508

AC XY:

35925

AN XY:

70724

show subpopulations

African (AFR)

AF:

0.383

AC:

15359

AN:

40052

American (AMR)

AF:

0.514

AC:

7369

AN:

14328

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1627

AN:

3346

East Asian (EAS)

AF:

0.569

AC:

2687

AN:

4724

South Asian (SAS)

AF:

0.467

AC:

2105

AN:

4506

European-Finnish (FIN)

AF:

0.614

AC:

6141

AN:

9994

Middle Eastern (MID)

AF:

0.450

AC:

126

AN:

280

European-Non Finnish (NFE)

AF:

0.562

AC:

36566

AN:

65058

Other (OTH)

AF:

0.490

AC:

984

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1741

3482

5224

6965

8706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.407

Hom.:

700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.5

(source)

DANN

Benign

0.76

PhyloP100

0.083

PromoterAI

0.058

Neutral

(source)

Mutation Taster

=300/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over