rs17823223

chr16-53965726-C-T

Variant summary

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

The NM_001080432.3(FTO):c.1364+31617C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,182 control chromosomes in the GnomAD database, including 907 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 0.093 (907 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1364+31617C>T		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1364+31617C>T		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14143 AN: 152060 Hom.: 907 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0929 AC: 14134 AN: 152178 Hom.: 907 Cov.: 32 AF XY: 0.0879 AC XY: 6539 AN XY: 74418

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.125

Alfa AF: 0.117 Hom.: 341

Bravo AF: 0.0943

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.3
Dann	Benign	0.72

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: rs17823223; hg19: chr16-53999638;