16-53778702-G-A

Variant names:

• chr16-53778702-G-A
• rs8057044
• NM_001080432.3:c.46-31438G>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.46-31438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,822 control chromosomes in the GnomAD database, including 22,972 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 0.53 (22972 hom., cov: 30)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 48 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.46-31438G>A		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.46-31438G>A		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-31438G>A		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-31438G>A		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.46-31438G>A		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.46-31438G>A		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81126 AN: 151704 Hom.: 22932 Cov.: 30

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.535 AC: 81215 AN: 151822 Hom.: 22972 Cov.: 30 AF XY: 0.528 AC XY: 39179 AN XY: 74218

African (AFR) AF: 0.724 AC: 29967 AN: 41384

American (AMR) AF: 0.426 AC: 6498 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3466

East Asian (EAS) AF: 0.240 AC: 1244 AN: 5174

South Asian (SAS) AF: 0.431 AC: 2073 AN: 4806

European-Finnish (FIN) AF: 0.446 AC: 4697 AN: 10528

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33009 AN: 67910

Other (OTH) AF: 0.521 AC: 1096 AN: 2102

Alfa AF: 0.527 Hom.: 14095

Bravo AF: 0.537

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.45
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: rs8057044; hg19: chr16-53812614;