NM_001080432.3:c.45+52040C>G

Variant names:

• chr16-53756269-C-G
• rs1861869
• NM_001080432.3:c.45+52040C>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.45+52040C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,998 control chromosomes in the GnomAD database, including 16,169 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 0.46 (16169 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.45+52040C>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.45+52040C>G		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69193 AN: 151882 Hom.: 16172 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.455 AC: 69206 AN: 151998 Hom.: 16169 Cov.: 32 AF XY: 0.452 AC XY: 33601 AN XY: 74258

African (AFR) AF: 0.391 AC: 16196 AN: 41458

American (AMR) AF: 0.449 AC: 6869 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1146 AN: 5170

South Asian (SAS) AF: 0.388 AC: 1871 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4775 AN: 10516

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34484 AN: 67952

Other (OTH) AF: 0.491 AC: 1035 AN: 2110

Alfa AF: 0.325 Hom.: 801

Bravo AF: 0.451

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.34
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: rs1861869; hg19: chr16-53790181;