16-54086472-C-T

Variant names:

• chr16-54086472-C-T
• rs11076017
• NM_001080432.3:c.1365-25290C>T

Variant summary

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

The NM_001080432.3(FTO):​c.1365-25290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,088 control chromosomes in the GnomAD database, including 16,413 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 0.44 (16413 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-25290C>T		intron_variant	Intron 8 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-25290C>T		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66642 AN: 151968 Hom.: 16422 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.438 AC: 66662 AN: 152088 Hom.: 16413 Cov.: 33 AF XY: 0.439 AC XY: 32654 AN XY: 74332

African (AFR) AF: 0.205 AC: 8500 AN: 41466

American (AMR) AF: 0.449 AC: 6864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1712 AN: 3464

East Asian (EAS) AF: 0.534 AC: 2762 AN: 5172

South Asian (SAS) AF: 0.453 AC: 2182 AN: 4818

European-Finnish (FIN) AF: 0.530 AC: 5605 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37534 AN: 67986

Other (OTH) AF: 0.469 AC: 990 AN: 2112

Alfa AF: 0.455 Hom.: 3204

Bravo AF: 0.421

Asia WGS AF: 0.442 AC: 1539 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.016
DANN	Benign	0.38
PhyloP100		-0.23
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: rs11076017; hg19: chr16-54120384;