dbSNP rs1421085: FTO:c.46-43098T>C (chr16-53767042-T-C) – 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.46-43098T>C variant causes a intron change. The variant allele was found at a frequency of 0.308 in 152,026 control chromosomes in the GnomAD database, including 8,801 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 0.31 ( 8801 hom., cov: 32)

Consequence

FTO
NM_001080432.3 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 4.50

Publications

665 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

FTO links:

LOC124903691 (HGNC:):

LOC124903691 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=-0.37).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTO	NM_001080432.3	MANE Select	c.46-43098T>C	intron	N/A	NP_001073901.1	Q9C0B1-1
FTO	NM_001363894.2		c.46-43098T>C	intron	N/A	NP_001350823.1
FTO	NM_001363891.2		c.46-43098T>C	intron	N/A	NP_001350820.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-43098T>C	intron	N/A	ENSP00000418823.1	Q9C0B1-1
FTO	ENST00000637969.1	TSL:5	c.46-43098T>C	intron	N/A	ENSP00000490516.1	A0A1B0GVH5
FTO	ENST00000918264.1		c.46-43098T>C	intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46878

AN:

151908

Hom.:

8806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.308

AC:

46862

AN:

152026

Hom.:

8801

Cov.:

AF XY:

0.309

AC XY:

22982

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.102

AC:

4231

AN:

41482

American (AMR)

AF:

0.289

AC:

4411

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1773

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

796

AN:

5170

South Asian (SAS)

AF:

0.332

AC:

1591

AN:

4796

European-Finnish (FIN)

AF:

0.423

AC:

4460

AN:

10548

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28328

AN:

67964

Other (OTH)

AF:

0.338

AC:

715

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1511

3022

4534

6045

7556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.375

Hom.:

50573

Bravo

AF:

0.285

Asia WGS

AF:

0.271

AC:

943

AN:

3478

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

OBESITY (BMIQ14), SUSCEPTIBILITY TO (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

4.5

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over