NM_001080432.3:c.124-999T>A

Variant names:

• chr16-53824865-T-A
• rs10852522
• NM_001080432.3:c.124-999T>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.124-999T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,040 control chromosomes in the GnomAD database, including 11,871 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 0.39 (11871 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.124-999T>A		intron_variant	Intron 2 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.124-999T>A		intron_variant	Intron 2 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59027 AN: 151922 Hom.: 11860 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.389 AC: 59076 AN: 152040 Hom.: 11871 Cov.: 32 AF XY: 0.384 AC XY: 28534 AN XY: 74302

African (AFR) AF: 0.376 AC: 15595 AN: 41444

American (AMR) AF: 0.439 AC: 6709 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1452 AN: 5170

South Asian (SAS) AF: 0.416 AC: 2004 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2332 AN: 10574

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27750 AN: 67958

Other (OTH) AF: 0.420 AC: 887 AN: 2114

Alfa AF: 0.383 Hom.: 1389

Bravo AF: 0.401

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.79
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: rs10852522; hg19: chr16-53858777;