16-53899635-C-T

Variant names:

• chr16-53899635-C-T
• rs1362570
• NM_001080432.3:c.1239+10684C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080432.3(FTO):​c.1239+10684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,100 control chromosomes in the GnomAD database, including 52,342 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 0.82 (52342 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1239+10684C>T		intron_variant	Intron 7 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1239+10684C>T		intron_variant	Intron 7 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124462 AN: 151980 Hom.: 52327 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.819 AC: 124520 AN: 152100 Hom.: 52342 Cov.: 31 AF XY: 0.821 AC XY: 60998 AN XY: 74334

African (AFR) AF: 0.601 AC: 24921 AN: 41444

American (AMR) AF: 0.892 AC: 13610 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3298 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4457 AN: 5162

South Asian (SAS) AF: 0.817 AC: 3939 AN: 4822

European-Finnish (FIN) AF: 0.901 AC: 9563 AN: 10608

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61769 AN: 68012

Other (OTH) AF: 0.858 AC: 1810 AN: 2110

Alfa AF: 0.898 Hom.: 97794

Bravo AF: 0.808

Asia WGS AF: 0.839 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		2.5
Mutation Taster		=99/1	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: rs1362570; hg19: chr16-53933547;