dbSNP rs6598045: ENSG00000251661:n.115+2255A>G (chr11-321001-A-G) – 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+2255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 647,542 control chromosomes in the GnomAD database, including 5,161 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 0.21 ( 1040 hom., cov: 32)

Exomes 𝑓: 0.18 ( 4121 hom. )

Consequence

ENSG00000251661
ENST00000602429.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.885

Publications

32 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM3	NM_021034.3 link	c.-188T>C		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.-188T>C		upstream_gene_variant		1	NM_021034.3	ENSP00000382707.4		Q01628

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

29273

AN:

142876

Hom.:

1042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.0639

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.0824

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.176

AC:

88842

AN:

504548

Hom.:

4121

Cov.:

AF XY:

0.182

AC XY:

48045

AN XY:

264384

show subpopulations

African (AFR)

AF:

0.317

AC:

4483

AN:

14160

American (AMR)

AF:

0.302

AC:

5979

AN:

19778

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

2205

AN:

13346

East Asian (EAS)

AF:

0.158

AC:

5171

AN:

32672

South Asian (SAS)

AF:

0.305

AC:

14493

AN:

47574

European-Finnish (FIN)

AF:

0.0840

AC:

2356

AN:

28038

Middle Eastern (MID)

AF:

0.224

AC:

450

AN:

2012

European-Non Finnish (NFE)

AF:

0.153

AC:

48807

AN:

319688

Other (OTH)

AF:

0.180

AC:

4898

AN:

27280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

3190

6381

9571

12762

15952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

960

1920

2880

3840

4800

<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:

0.205

AC:

29330

AN:

142994

Hom.:

1040

Cov.:

AF XY:

0.205

AC XY:

14350

AN XY:

70018

show subpopulations

African (AFR)

AF:

0.309

AC:

12065

AN:

39058

American (AMR)

AF:

0.259

AC:

3776

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

556

AN:

3272

East Asian (EAS)

AF:

0.172

AC:

884

AN:

5134

South Asian (SAS)

AF:

0.286

AC:

1318

AN:

4602

European-Finnish (FIN)

AF:

0.0824

AC:

824

AN:

10000

Middle Eastern (MID)

AF:

0.234

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.148

AC:

9361

AN:

63286

Other (OTH)

AF:

0.214

AC:

428

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

914

1828

2741

3655

4569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.186

Hom.:

115

Asia WGS

AF:

0.234

AC:

816

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

(source)

DANN

Benign

0.55

PhyloP100

-0.89

PromoterAI

0.20

Neutral

(source)

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

Computational scores

Splicing

Publications

Other links and lift over