NM_001080432.3:c.124-864C>T

Variant names:

• chr16-53825000-C-T
• rs11075997
• NM_001080432.3:c.124-864C>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.124-864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,944 control chromosomes in the GnomAD database, including 11,755 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 (11755 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.124-864C>T		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.124-864C>T		intron_variant	Intron 2 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58563 AN: 151824 Hom.: 11744 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.386 AC: 58613 AN: 151944 Hom.: 11755 Cov.: 32 AF XY: 0.381 AC XY: 28297 AN XY: 74276

African (AFR) AF: 0.377 AC: 15598 AN: 41408

American (AMR) AF: 0.438 AC: 6695 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1712 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5172

South Asian (SAS) AF: 0.415 AC: 1995 AN: 4810

European-Finnish (FIN) AF: 0.220 AC: 2316 AN: 10550

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27737 AN: 67952

Other (OTH) AF: 0.417 AC: 878 AN: 2106

Alfa AF: 0.414 Hom.: 22133

Bravo AF: 0.397

Asia WGS AF: 0.339 AC: 1182 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	0.69
DANN	Benign	0.31
PhyloP100		-0.99
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: rs11075997; hg19: chr16-53858912;