NM_001080432.3:c.46-41558C>T

Variant names:

• chr16-53768582-C-T
• rs11642015
• NM_001080432.3:c.46-41558C>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.46-41558C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,014 control chromosomes in the GnomAD database, including 8,799 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 0.31 (8799 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 74 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-41558C>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.46-41558C>T		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46722 AN: 151896 Hom.: 8803 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.307 AC: 46707 AN: 152014 Hom.: 8799 Cov.: 32 AF XY: 0.308 AC XY: 22907 AN XY: 74284

African (AFR) AF: 0.0981 AC: 4071 AN: 41494

American (AMR) AF: 0.288 AC: 4400 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1773 AN: 3472

East Asian (EAS) AF: 0.154 AC: 795 AN: 5160

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4818

European-Finnish (FIN) AF: 0.424 AC: 4477 AN: 10554

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28327 AN: 67930

Other (OTH) AF: 0.336 AC: 710 AN: 2110

Alfa AF: 0.322 Hom.: 4807

Bravo AF: 0.283

Asia WGS AF: 0.270 AC: 940 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		0.16
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: rs11642015; hg19: chr16-53802494;