rs3751812

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001080432.3(FTO):​c.46-25592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,008 control chromosomes in the GnomAD database, including 8,219 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 0.30 ( 8219 hom., cov: 31)

Consequence

FTO
NM_001080432.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.592
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FTONM_001080432.3 linkuse as main transcriptc.46-25592G>T intron_variant ENST00000471389.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FTOENST00000471389.6 linkuse as main transcriptc.46-25592G>T intron_variant 1 NM_001080432.3 P1Q9C0B1-1

Frequencies

GnomAD3 genomes
AF:
0.298
AC:
45326
AN:
151890
Hom.:
8221
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0996
Gnomad AMI
AF:
0.462
Gnomad AMR
AF:
0.274
Gnomad ASJ
AF:
0.501
Gnomad EAS
AF:
0.152
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.399
Gnomad MID
AF:
0.364
Gnomad NFE
AF:
0.406
Gnomad OTH
AF:
0.321
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.298
AC:
45312
AN:
152008
Hom.:
8219
Cov.:
31
AF XY:
0.298
AC XY:
22128
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.0993
Gnomad4 AMR
AF:
0.274
Gnomad4 ASJ
AF:
0.501
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.312
Gnomad4 FIN
AF:
0.399
Gnomad4 NFE
AF:
0.406
Gnomad4 OTH
AF:
0.322
Alfa
AF:
0.384
Hom.:
16948
Bravo
AF:
0.276
Asia WGS
AF:
0.266
AC:
927
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Benign
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3751812; hg19: chr16-53818460; API