rs13334933

Variant names:

• chr16-53761724-A-G
• rs13334933
• NM_001080432.3:c.46-48416A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-53761724-A-G
• chr16-53761724-A-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.46-48416A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,966 control chromosomes in the GnomAD database, including 9,632 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 0.30 (9632 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 14 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

LOC124903691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-48416A>G		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.46-48416A>G		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45595 AN: 151848 Hom.: 9599 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.301 AC: 45677 AN: 151966 Hom.: 9632 Cov.: 32 AF XY: 0.294 AC XY: 21831 AN XY: 74280

African (AFR) AF: 0.601 AC: 24915 AN: 41424

American (AMR) AF: 0.176 AC: 2686 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3466

East Asian (EAS) AF: 0.296 AC: 1520 AN: 5138

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4818

European-Finnish (FIN) AF: 0.142 AC: 1501 AN: 10564

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12295 AN: 67978

Other (OTH) AF: 0.279 AC: 588 AN: 2110

Alfa AF: 0.221 Hom.: 13409

Bravo AF: 0.315

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.80
PhyloP100		-2.1
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: rs13334933; hg19: chr16-53795636;