rs16952777

chr16-54003710-G-Cchr16-54003710-G-T

Variant summary

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

The NM_001080432.3(FTO):c.1364+69601G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,000 control chromosomes in the GnomAD database, including 7,002 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 0.28 (7002 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1364+69601G>C		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1364+69601G>C		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42868 AN: 151882 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.282 AC: 42849 AN: 152000 Hom.: 7002 Cov.: 32 AF XY: 0.281 AC XY: 20849 AN XY: 74276

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.325

Alfa AF: 0.301 Hom.: 929

Bravo AF: 0.282

Asia WGS AF: 0.339 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.80
Dann	Benign	0.57

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: rs16952777; hg19: chr16-54037622;