16-53841572-G-T

Variant names:

• chr16-53841572-G-T
• rs8053367
• NM_001080432.3:c.752-2583G>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.752-2583G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,958 control chromosomes in the GnomAD database, including 16,222 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 0.45 (16222 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.752-2583G>T		intron_variant	Intron 3 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.752-2583G>T		intron_variant	Intron 3 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69047 AN: 151840 Hom.: 16204 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.455 AC: 69113 AN: 151958 Hom.: 16222 Cov.: 32 AF XY: 0.452 AC XY: 33577 AN XY: 74290

African (AFR) AF: 0.533 AC: 22080 AN: 41422

American (AMR) AF: 0.470 AC: 7180 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2583 AN: 5142

South Asian (SAS) AF: 0.552 AC: 2665 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2506 AN: 10578

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28800 AN: 67942

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.426 Hom.: 2405

Bravo AF: 0.471

Asia WGS AF: 0.542 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.50
DANN	Benign	0.60
PhyloP100		-1.2
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: rs8053367; hg19: chr16-53875484;