16-54020166-G-A

Variant names:

• chr16-54020166-G-A
• rs1107355
• NM_001080432.3:c.1364+86057G>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.1364+86057G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,970 control chromosomes in the GnomAD database, including 7,713 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 (7713 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.46
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1364+86057G>A		intron_variant	Intron 8 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1364+86057G>A		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46815 AN: 151852 Hom.: 7704 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.308 AC: 46877 AN: 151970 Hom.: 7713 Cov.: 32 AF XY: 0.313 AC XY: 23269 AN XY: 74288

African (AFR) AF: 0.365 AC: 15100 AN: 41414

American (AMR) AF: 0.387 AC: 5913 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1966 AN: 5174

South Asian (SAS) AF: 0.440 AC: 2121 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10552

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17010 AN: 67960

Other (OTH) AF: 0.297 AC: 627 AN: 2108

Alfa AF: 0.285 Hom.: 2194

Bravo AF: 0.318

Asia WGS AF: 0.415 AC: 1439 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0010
DANN	Benign	0.64
PhyloP100		-5.5
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: rs1107355; hg19: chr16-54054078;