16-54086472-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.1365-25290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,088 control chromosomes in the GnomAD database, including 16,413 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 0.44 (16413 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1365-25290C>T		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1365-25290C>T		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66642 AN: 151968 Hom.: 16422 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66662 AN: 152088 Hom.: 16413 Cov.: 33 AF XY: 0.439 AC XY: 32654 AN XY: 74332

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.469

Alfa AF: 0.462 Hom.: 3192

Bravo AF: 0.421

Asia WGS AF: 0.442 AC: 1539 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.016
Dann	Benign	0.38

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: rs11076017; hg19: chr16-54120384;