NM_001080432.3:c.1239+16540G>A

Variant names:

• chr16-53905491-G-A
• rs9929152
• NM_001080432.3:c.1239+16540G>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.1239+16540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,948 control chromosomes in the GnomAD database, including 36,471 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 0.67 (36471 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1239+16540G>A		intron_variant	Intron 7 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1239+16540G>A		intron_variant	Intron 7 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 101997 AN: 151828 Hom.: 36469 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.671 AC: 102016 AN: 151948 Hom.: 36471 Cov.: 31 AF XY: 0.678 AC XY: 50351 AN XY: 74278

African (AFR) AF: 0.402 AC: 16617 AN: 41326

American (AMR) AF: 0.748 AC: 11427 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2637 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5065 AN: 5184

South Asian (SAS) AF: 0.788 AC: 3792 AN: 4814

European-Finnish (FIN) AF: 0.828 AC: 8772 AN: 10590

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51389 AN: 67970

Other (OTH) AF: 0.678 AC: 1433 AN: 2114

Alfa AF: 0.739 Hom.: 86299

Bravo AF: 0.654

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.98
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: rs9929152; hg19: chr16-53939403;