rs17818902

Variant names:

• chr16-53837894-T-G
• rs17818902
• NM_001080432.3:c.752-6261T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.752-6261T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,048 control chromosomes in the GnomAD database, including 5,805 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 0.27 (5805 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• lethal polymalformative syndrome, Boissel type

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.752-6261T>G		intron_variant	Intron 3 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.752-6261T>G		intron_variant	Intron 3 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40390 AN: 151930 Hom.: 5801 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.266 AC: 40434 AN: 152048 Hom.: 5805 Cov.: 32 AF XY: 0.266 AC XY: 19766 AN XY: 74334

African (AFR) AF: 0.368 AC: 15246 AN: 41452

American (AMR) AF: 0.263 AC: 4016 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3468

East Asian (EAS) AF: 0.178 AC: 919 AN: 5168

South Asian (SAS) AF: 0.345 AC: 1659 AN: 4808

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10590

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15171 AN: 67986

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.246 Hom.: 845

Bravo AF: 0.278

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.53
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17818902; hg19: chr16-53871806;