16-53800696-G-A

Variant names:

• chr16-53800696-G-A
• rs72805612
• NM_001080432.3:c.46-9444G>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.46-9444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,728 control chromosomes in the GnomAD database, including 8,553 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 (8553 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 17 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-9444G>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.46-9444G>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46343 AN: 151610 Hom.: 8554 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.305 AC: 46329 AN: 151728 Hom.: 8553 Cov.: 33 AF XY: 0.304 AC XY: 22493 AN XY: 74084

African (AFR) AF: 0.102 AC: 4222 AN: 41520

American (AMR) AF: 0.280 AC: 4266 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1705 AN: 3452

East Asian (EAS) AF: 0.159 AC: 822 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 3983 AN: 10460

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28471 AN: 67762

Other (OTH) AF: 0.332 AC: 700 AN: 2110

Alfa AF: 0.352 Hom.: 1406

Bravo AF: 0.286

Asia WGS AF: 0.278 AC: 964 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		0.33
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: rs72805612; hg19: chr16-53834608;