16-54119187-A-T

Position:

• chr16-54119187-A-T

Variant summary

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

The NM_001080432.3(FTO):​c.*7272A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,094 control chromosomes in the GnomAD database, including 9,456 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 0.32 (9456 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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 (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*7272A>T		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.*7272A>T		3_prime_UTR_variant	9/9	1	NM_001080432.3	ENSP00000418823.1
FTO	ENST00000637969.1	c.1492+7298A>T		intron_variant		5		ENSP00000490516.1
FTO	ENST00000612285.2	c.517+7298A>T		intron_variant		5		ENSP00000490300.1
FTO	ENST00000637845.1	n.*316+381A>T		intron_variant		5		ENSP00000489638.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48512 AN: 151970 Hom.: 9460 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.319 AC: 48502 AN: 152090 Hom.: 9456 Cov.: 32 AF XY: 0.325 AC XY: 24157 AN XY: 74306

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.326

Alfa AF: 0.348 Hom.: 1248

Bravo AF: 0.303

Asia WGS AF: 0.334 AC: 1160 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	1.9
DANN	Benign	0.70

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: rs2075205; hg19: chr16-54153099;