rs11076022

Positions:

• chr16-54117066-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.*5151A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,096 control chromosomes in the GnomAD database, including 10,141 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 0.34 (10140 hom., cov: 32)
  • Exomes 𝑓: 0.31 (1 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.*5151A>G		3_prime_UTR_variant	9/9	ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.*5151A>G		3_prime_UTR_variant	9/9	1	NM_001080432.3	P1
FTO	ENST00000612285.2	c.517+5177A>G		intron_variant		5
FTO	ENST00000637969.1	c.1492+5177A>G		intron_variant		5
FTO	ENST00000637845.1	c.1493-1315A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52235 AN: 151962 Hom.: 10139 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 AFR exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.400

GnomAD4 genome AF: 0.344 AC: 52258 AN: 152080 Hom.: 10140 Cov.: 32 AF XY: 0.350 AC XY: 26019 AN XY: 74346

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.345

Alfa AF: 0.380 Hom.: 3583

Bravo AF: 0.332

Asia WGS AF: 0.357 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs11076022; hg19: chr16-54150978;