dbSNP rs2192872: FTO:c.1365-71047T>C (chr16-54040715-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001080432.3(FTO):c.1365-71047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,048 control chromosomes in the GnomAD database, including 20,556 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 0.48 ( 20550 hom., cov: 32)

Exomes 𝑓: 0.57 ( 6 hom. )

Consequence

FTO
NM_001080432.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.34

Publications

15 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:

ENSG00000261049 (HGNC:):

ENSG00000261049 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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
FTO	NM_001080432.3	MANE Select	c.1365-71047T>C	intron	N/A	NP_001073901.1
FTO	NM_001363894.2		c.1428-71047T>C	intron	N/A	NP_001350823.1
FTO	NM_001363891.2		c.1395-71047T>C	intron	N/A	NP_001350820.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FTO	ENST00000471389.6	TSL:1 MANE Select	c.1365-71047T>C	intron	N/A	ENSP00000418823.1
FTO	ENST00000268349.7	TSL:1	c.97+55761T>C	intron	N/A	ENSP00000268349.7
FTO	ENST00000463855.1	TSL:1	c.231-71047T>C	intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73540

AN:

151900

Hom.:

20493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.567

AC:

AN:

Hom.:

Cov.:

AF XY:

0.550

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.643

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.485

AC:

73656

AN:

152018

Hom.:

20550

Cov.:

AF XY:

0.491

AC XY:

36467

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.765

AC:

31748

AN:

41496

American (AMR)

AF:

0.468

AC:

7156

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1003

AN:

3468

East Asian (EAS)

AF:

0.533

AC:

2746

AN:

5156

South Asian (SAS)

AF:

0.515

AC:

2474

AN:

4808

European-Finnish (FIN)

AF:

0.434

AC:

4578

AN:

10542

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.333

AC:

22658

AN:

67954

Other (OTH)

AF:

0.420

AC:

887

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1704

3408

5112

6816

8520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.439

Hom.:

2903

Bravo

AF:

0.497

Asia WGS

AF:

0.506

AC:

1758

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

(source)

DANN

Benign

0.44

PhyloP100

-2.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over