NM_001080432.3:c.46-37772C>G

Variant names:

• chr16-53772368-C-G
• rs9922047
• NM_001080432.3:c.46-37772C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.46-37772C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,822 control chromosomes in the GnomAD database, including 26,043 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 0.58 (26043 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 30 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-37772C>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.46-37772C>G		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87452 AN: 151704 Hom.: 26005 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.577 AC: 87537 AN: 151822 Hom.: 26043 Cov.: 31 AF XY: 0.574 AC XY: 42586 AN XY: 74200

African (AFR) AF: 0.728 AC: 30134 AN: 41406

American (AMR) AF: 0.481 AC: 7326 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2108 AN: 3466

East Asian (EAS) AF: 0.646 AC: 3326 AN: 5146

South Asian (SAS) AF: 0.492 AC: 2376 AN: 4828

European-Finnish (FIN) AF: 0.511 AC: 5394 AN: 10556

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35087 AN: 67890

Other (OTH) AF: 0.566 AC: 1192 AN: 2106

Alfa AF: 0.566 Hom.: 3147

Bravo AF: 0.580

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.43
PhyloP100		-0.70
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: rs9922047; hg19: chr16-53806280;