16-54067549-G-T

Variant names:

• chr16-54067549-G-T
• rs12600060
• NM_001080432.3:c.1365-44213G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080432.3(FTO):​c.1365-44213G>T variant causes a intron change. The variant allele was found at a frequency of 0.198 in 152,204 control chromosomes in the GnomAD database, including 3,717 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 0.20 (3717 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42
• Publications: 9 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

LOC105371271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-44213G>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.1365-44213G>T		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30126 AN: 152086 Hom.: 3721 Cov.: 33

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.198 AC: 30114 AN: 152204 Hom.: 3717 Cov.: 33 AF XY: 0.197 AC XY: 14631 AN XY: 74416

African (AFR) AF: 0.0596 AC: 2478 AN: 41564

American (AMR) AF: 0.243 AC: 3714 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2372 AN: 5168

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16926 AN: 67992

Other (OTH) AF: 0.240 AC: 505 AN: 2106

Alfa AF: 0.237 Hom.: 2612

Bravo AF: 0.201

Asia WGS AF: 0.312 AC: 1086 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		5.4
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: rs12600060; hg19: chr16-54101461;