16-54121830-T-C

Position:

• chr16-54121830-T-C

Variant summary

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

The NM_001080432.3(FTO):​c.*9915T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,032 control chromosomes in the GnomAD database, including 7,738 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 0.31 (7737 hom., cov: 31)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*9915T>C		3_prime_UTR_variant	9/9	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.*9915T>C		3_prime_UTR_variant	9/9	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47328 AN: 151900 Hom.: 7717 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.312 AC: 47382 AN: 152018 Hom.: 7737 Cov.: 31 AF XY: 0.319 AC XY: 23662 AN XY: 74290

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.323

Alfa AF: 0.323 Hom.: 8282

Bravo AF: 0.303

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.53

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: rs16953089; hg19: chr16-54155742;