rs9939973

Variant names:

• chr16-53766656-G-A
• rs9939973
• NM_001080432.3:c.46-43484G>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.46-43484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,016 control chromosomes in the GnomAD database, including 13,463 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 (13463 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 89 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=-0.81).
• 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.46-43484G>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.46-43484G>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63351 AN: 151896 Hom.: 13453 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.417 AC: 63394 AN: 152016 Hom.: 13463 Cov.: 32 AF XY: 0.415 AC XY: 30811 AN XY: 74270

African (AFR) AF: 0.423 AC: 17539 AN: 41466

American (AMR) AF: 0.347 AC: 5303 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1028 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1985 AN: 4812

European-Finnish (FIN) AF: 0.432 AC: 4563 AN: 10562

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29627 AN: 67956

Other (OTH) AF: 0.417 AC: 880 AN: 2108

Alfa AF: 0.424 Hom.: 38984

Bravo AF: 0.404

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	-0.81
CADD	Benign	6.4
DANN	Benign	0.65
PhyloP100		1.7
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: rs9939973; hg19: chr16-53800568;