Genetic Variant FTO:c.*6793G>C (chr16-54118708-G-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.*6793G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,902 control chromosomes in the GnomAD database, including 11,681 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 0.38 ( 11678 hom., cov: 31)

Exomes 𝑓: 0.42 ( 3 hom. )

Consequence

FTO
NM_001080432.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.704

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3 link	c.*6793G>C		3_prime_UTR_variant	Exon 9 of 9	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.*6793G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001080432.3	ENSP00000418823.1		Q9C0B1-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58220

AN:

151748

Hom.:

11671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.418

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.421

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

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:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.469

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.384

AC:

58268

AN:

151864

Hom.:

11678

Cov.:

AF XY:

0.391

AC XY:

28989

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.271

AC:

11234

AN:

41386

American (AMR)

AF:

0.400

AC:

6109

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1386

AN:

3470

East Asian (EAS)

AF:

0.542

AC:

2788

AN:

5144

South Asian (SAS)

AF:

0.387

AC:

1863

AN:

4814

European-Finnish (FIN)

AF:

0.504

AC:

5305

AN:

10532

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.418

AC:

28403

AN:

67952

Other (OTH)

AF:

0.381

AC:

801

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1783

3566

5348

7131

8914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.399

Hom.:

1534

Bravo

AF:

0.373

Asia WGS

AF:

0.424

AC:

1472

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.64

(source)

DANN

Benign

0.72

PhyloP100

-0.70

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