rs17217144

Variant names:

• chr16-53756850-C-T
• rs17217144
• NM_001080432.3:c.45+52621C>T

Variant summary

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

The NM_001080432.3(FTO):​c.45+52621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,978 control chromosomes in the GnomAD database, including 12,256 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 0.39 (12256 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 10 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

LOC124903691 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.45+52621C>T		intron_variant	Intron 1 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.45+52621C>T		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59340 AN: 151860 Hom.: 12263 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.390 AC: 59339 AN: 151978 Hom.: 12256 Cov.: 33 AF XY: 0.389 AC XY: 28884 AN XY: 74268

African (AFR) AF: 0.268 AC: 11104 AN: 41482

American (AMR) AF: 0.392 AC: 5979 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1972 AN: 3468

East Asian (EAS) AF: 0.188 AC: 973 AN: 5180

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4828

European-Finnish (FIN) AF: 0.444 AC: 4668 AN: 10516

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31624 AN: 67934

Other (OTH) AF: 0.426 AC: 899 AN: 2108

Alfa AF: 0.424 Hom.: 4254

Bravo AF: 0.383

Asia WGS AF: 0.254 AC: 883 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		1.2
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: rs17217144; hg19: chr16-53790762;