rs9937053

Variant names:

• chr16-53765595-G-A
• rs9937053
• NM_001080432.3:c.46-44545G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-53765595-G-A
• chr16-53765595-G-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.46-44545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 150,544 control chromosomes in the GnomAD database, including 13,303 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 0.42 (13303 hom., cov: 28)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 55 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-44545G>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.46-44545G>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62626 AN: 150442 Hom.: 13295 Cov.: 28

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.416 AC: 62660 AN: 150544 Hom.: 13303 Cov.: 28 AF XY: 0.414 AC XY: 30351 AN XY: 73380

African (AFR) AF: 0.421 AC: 17221 AN: 40878

American (AMR) AF: 0.349 AC: 5281 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1903 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1003 AN: 5114

South Asian (SAS) AF: 0.413 AC: 1967 AN: 4768

European-Finnish (FIN) AF: 0.423 AC: 4274 AN: 10094

Middle Eastern (MID) AF: 0.399 AC: 115 AN: 288

European-Non Finnish (NFE) AF: 0.436 AC: 29577 AN: 67792

Other (OTH) AF: 0.417 AC: 872 AN: 2092

Alfa AF: 0.412 Hom.: 10267

Bravo AF: 0.405

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		0.029
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: rs9937053; hg19: chr16-53799507;