rs17219084

Variant names:

• chr16-53821688-A-G
• rs17219084
• NM_001080432.3:c.124-4176A>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.124-4176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,008 control chromosomes in the GnomAD database, including 8,156 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 0.32 (8156 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.124-4176A>G		intron_variant	Intron 2 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.124-4176A>G		intron_variant	Intron 2 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48076 AN: 151890 Hom.: 8155 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.316 AC: 48091 AN: 152008 Hom.: 8156 Cov.: 32 AF XY: 0.311 AC XY: 23109 AN XY: 74296

African (AFR) AF: 0.230 AC: 9527 AN: 41468

American (AMR) AF: 0.347 AC: 5292 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1117 AN: 5150

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4812

European-Finnish (FIN) AF: 0.210 AC: 2225 AN: 10588

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25532 AN: 67950

Other (OTH) AF: 0.358 AC: 755 AN: 2106

Alfa AF: 0.366 Hom.: 20906

Bravo AF: 0.319

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.84
PhyloP100		0.13
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: rs17219084; hg19: chr16-53855600;