dbSNP rs1588413: FTO:c.*3705G>A (chr16-54115620-G-A) – 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.*3705G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,962 control chromosomes in the GnomAD database, including 1,999 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 0.15 ( 1998 hom., cov: 31)

Exomes 𝑓: 0.11 ( 1 hom. )

Consequence

FTO
NM_001080432.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.590

Publications

11 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3 link	c.*3705G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000471389.6	NP_001073901.1	Q9C0B1-1B3KU60Q99770

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FTO	ENST00000471389.6 link	c.*3705G>A	3_prime_UTR_variant	Exon 9 of 9	1	NM_001080432.3	ENSP00000418823.1	Q9C0B1-1
FTO	ENST00000637969.1 link	c.1492+3731G>A	intron_variant	Intron 9 of 10	5		ENSP00000490516.1	A0A1B0GVH5
FTO	ENST00000612285.2 link	c.517+3731G>A	intron_variant	Intron 4 of 4	5		ENSP00000490300.1	A0A1B0GUY7
FTO	ENST00000637845.1 link	n.1493-2761G>A	intron_variant	Intron 9 of 10	5		ENSP00000489638.1	A0A1B0GTC3

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22505

AN:

151602

Hom.:

1991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.108

AC:

AN:

240

Hom.:

Cov.:

AF XY:

0.112

AC XY:

AN XY:

170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.121

AC:

AN:

198

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.148

AC:

22520

AN:

151722

Hom.:

1998

Cov.:

AF XY:

0.151

AC XY:

11185

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.0569

AC:

2358

AN:

41418

American (AMR)

AF:

0.198

AC:

3017

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

659

AN:

3460

East Asian (EAS)

AF:

0.290

AC:

1463

AN:

5044

South Asian (SAS)

AF:

0.248

AC:

1185

AN:

4782

European-Finnish (FIN)

AF:

0.169

AC:

1788

AN:

10554

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11454

AN:

67892

Other (OTH)

AF:

0.175

AC:

369

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

907

1814

2722

3629

4536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.166

Hom.:

2419

Bravo

AF:

0.147

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.47

(source)

DANN

Benign

0.80

PhyloP100

-0.59

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