dbSNP rs3888188: ENSG00000251661:n.115+2271A>C (chr11-321017-A-C) – 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+2271A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.26 ( 1245 hom., cov: 32)

Exomes 𝑓: 0.22 ( 6888 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000251661
ENST00000602429.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

14 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=-0.79).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM3	NM_021034.3 link	c.-204T>G		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.-204T>G		upstream_gene_variant		1	NM_021034.3	ENSP00000382707.4		Q01628

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

27387

AN:

107176

Hom.:

1247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.173

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.220

AC:

72919

AN:

330746

Hom.:

6888

Cov.:

AF XY:

0.226

AC XY:

39211

AN XY:

173534

show subpopulations

African (AFR)

AF:

0.242

AC:

1953

AN:

8084

American (AMR)

AF:

0.314

AC:

3920

AN:

12474

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

1319

AN:

8396

East Asian (EAS)

AF:

0.693

AC:

19409

AN:

27990

South Asian (SAS)

AF:

0.334

AC:

10257

AN:

30752

European-Finnish (FIN)

AF:

0.157

AC:

3185

AN:

20232

Middle Eastern (MID)

AF:

0.187

AC:

247

AN:

1324

European-Non Finnish (NFE)

AF:

0.142

AC:

28861

AN:

203322

Other (OTH)

AF:

0.207

AC:

3768

AN:

18172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

3118

6236

9354

12472

15590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

620

1240

1860

2480

3100

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.256

AC:

27412

AN:

107254

Hom.:

1245

Cov.:

AF XY:

0.263

AC XY:

13888

AN XY:

52714

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.289

AC:

7541

AN:

26136

American (AMR)

AF:

0.311

AC:

3281

AN:

10542

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

533

AN:

2320

East Asian (EAS)

AF:

0.682

AC:

3225

AN:

4726

South Asian (SAS)

AF:

0.377

AC:

1281

AN:

3402

European-Finnish (FIN)

AF:

0.197

AC:

1651

AN:

8370

Middle Eastern (MID)

AF:

0.163

AC:

AN:

178

European-Non Finnish (NFE)

AF:

0.190

AC:

9374

AN:

49458

Other (OTH)

AF:

0.265

AC:

386

AN:

1458

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

1666

3333

4999

6666

8332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.220

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.0

(source)

DANN

Benign

0.86

PhyloP100

-2.0

PromoterAI

0.0070

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

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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