dbSNP rs16952730: FTO:c.1364+50900G>A (chr16-53985009-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001080432.3(FTO):c.1364+50900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 455,684 control chromosomes in the GnomAD database, including 25,315 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 0.31 ( 7829 hom., cov: 31)

Exomes 𝑓: 0.33 ( 17486 hom. )

Consequence

FTO
NM_001080432.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

14 publications found

Variant links:

Genes affected

FTO (HGNC:24678): (FTO alpha-ketoglutarate dependent dioxygenase) This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

FTO Gene-Disease associations (from GenCC):

lethal polymalformative syndrome, Boissel type
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

FTO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3 link	c.1364+50900G>A		intron_variant	Intron 8 of 8	ENST00000471389.6	NP_001073901.1	Q9C0B1-1B3KU60Q99770

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6 link	c.1364+50900G>A		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1		Q9C0B1-1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46843

AN:

151746

Hom.:

7820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.334

GnomAD4 exome

AF:

0.325

AC:

98750

AN:

303818

Hom.:

17486

AF XY:

0.322

AC XY:

55741

AN XY:

172994

show subpopulations

African (AFR)

AF:

0.274

AC:

2351

AN:

8580

American (AMR)

AF:

0.461

AC:

12531

AN:

27166

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

3598

AN:

10764

East Asian (EAS)

AF:

0.719

AC:

6616

AN:

9206

South Asian (SAS)

AF:

0.316

AC:

18838

AN:

59586

European-Finnish (FIN)

AF:

0.281

AC:

3593

AN:

12768

Middle Eastern (MID)

AF:

0.333

AC:

924

AN:

2776

European-Non Finnish (NFE)

AF:

0.287

AC:

45602

AN:

158752

Other (OTH)

AF:

0.330

AC:

4697

AN:

14220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3277

6553

9830

13106

16383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.309

AC:

46870

AN:

151866

Hom.:

7829

Cov.:

AF XY:

0.313

AC XY:

23227

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.262

AC:

10842

AN:

41396

American (AMR)

AF:

0.397

AC:

6059

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1137

AN:

3470

East Asian (EAS)

AF:

0.718

AC:

3688

AN:

5138

South Asian (SAS)

AF:

0.328

AC:

1578

AN:

4806

European-Finnish (FIN)

AF:

0.289

AC:

3052

AN:

10552

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.287

AC:

19477

AN:

67938

Other (OTH)

AF:

0.335

AC:

702

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1578

3156

4734

6312

7890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.300

Hom.:

8880

Bravo

AF:

0.319

Asia WGS

AF:

0.481

AC:

1670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.7

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