NM_001080432.3:c.46-24281G>A

Variant names:

• chr16-53785859-G-A
• rs11075988
• NM_001080432.3:c.46-24281G>A

Variant summary

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

The NM_001080432.3(FTO):​c.46-24281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 150,032 control chromosomes in the GnomAD database, including 12,850 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 0.41 (12850 hom., cov: 26)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 16 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-24281G>A		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.46-24281G>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61063 AN: 149920 Hom.: 12838 Cov.: 26

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.407 AC: 61098 AN: 150032 Hom.: 12850 Cov.: 26 AF XY: 0.403 AC XY: 29433 AN XY: 73108

African (AFR) AF: 0.479 AC: 19482 AN: 40714

American (AMR) AF: 0.315 AC: 4745 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1749 AN: 3456

East Asian (EAS) AF: 0.151 AC: 771 AN: 5106

South Asian (SAS) AF: 0.313 AC: 1486 AN: 4746

European-Finnish (FIN) AF: 0.395 AC: 3964 AN: 10044

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27547 AN: 67608

Other (OTH) AF: 0.397 AC: 824 AN: 2078

Alfa AF: 0.427 Hom.: 1848

Bravo AF: 0.401

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.80
PhyloP100		-1.7
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: rs11075988; hg19: chr16-53819771;