16-53814649-A-G

Position:

• chr16-53814649-A-G

Variant summary

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

The NM_001080432.3(FTO):​c.123+4432A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,180 control chromosomes in the GnomAD database, including 36,598 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 0.68 (36534 hom., cov: 30)
  • Exomes 𝑓: 0.66 (64 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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]

FTO (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.123+4432A>G		intron_variant		ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.123+4432A>G		intron_variant		1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103805 AN: 151810 Hom.: 36490 Cov.: 30

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.659 AC: 166 AN: 252 Hom.: 64 Cov.: 0 AF XY: 0.654 AC XY: 119 AN XY: 182

Gnomad4 AFR exome AF: 0.875

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.684 AC: 103904 AN: 151928 Hom.: 36534 Cov.: 30 AF XY: 0.682 AC XY: 50602 AN XY: 74224

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.676

Alfa AF: 0.653 Hom.: 11328

Bravo AF: 0.686

Asia WGS AF: 0.757 AC: 2631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.72

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: rs1861867; hg19: chr16-53848561;