rs2287142

Positions:

• chr16-53911439-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000463855.1(FTO):​c.60G>A​(p.Lys20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 703,074 control chromosomes in the GnomAD database, including 3,228 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 0.029 (383 hom., cov: 32)
  • Exomes 𝑓: 0.045 (2845 hom.)
• Consequence: FTO ENST00000463855.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-0.767 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1239+22488G>A		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1239+22488G>A		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4352 AN: 152174 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0743 AC: 10205 AN: 137312 Hom.: 1186 AF XY: 0.0679 AC XY: 5065 AN XY: 74574

Gnomad AFR exome AF: 0.00386

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.000962

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.0687

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.0435

GnomAD4 exome AF: 0.0450 AC: 24782 AN: 550780 Hom.: 2845 Cov.: 0 AF XY: 0.0444 AC XY: 13249 AN XY: 298148

Gnomad4 AFR exome AF: 0.00386

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.0665

Gnomad4 FIN exome AF: 0.0281

Gnomad4 NFE exome AF: 0.00300

Gnomad4 OTH exome AF: 0.0384

GnomAD4 genome AF: 0.0287 AC: 4364 AN: 152294 Hom.: 383 Cov.: 32 AF XY: 0.0331 AC XY: 2463 AN XY: 74462

Gnomad4 AFR AF: 0.00452

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.0790

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0107 Hom.: 33

Bravo AF: 0.0375

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.040
DANN	Benign	0.31

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: rs2287142; hg19: chr16-53945351; COSMIC: COSV67110764;