16-53779455-T-G

Variant summary

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

The NM_001080432.3(FTO):c.46-30685T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,026 control chromosomes in the GnomAD database, including 11,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11497 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176

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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.46-30685T>G		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.46-30685T>G		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58339 AN: 151908 Hom.: 11489 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.384 AC: 58367 AN: 152026 Hom.: 11497 Cov.: 32 AF XY: 0.381 AC XY: 28308 AN XY: 74304

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.385

Alfa AF: 0.389 Hom.: 22611

Bravo AF: 0.373

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	8.9
Dann	Benign	0.65

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: rs17817449; hg19: chr16-53813367;