16-53917749-T-C

Variant names:

• chr16-53917749-T-C
• rs4783824
• NM_001080432.3:c.1240-16236T>C

Variant summary

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

The NM_001080432.3(FTO):​c.1240-16236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 150,772 control chromosomes in the GnomAD database, including 61,860 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 0.91 (61860 hom., cov: 26)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 4 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1240-16236T>C		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1303-16236T>C		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1270-16236T>C		intron	N/A	NP_001350820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1240-16236T>C		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000463855.1	TSL:1	c.105+6265T>C		intron	N/A	ENSP00000417843.1	Q9C0B1-2
	FTO	ENST00000637969.1	TSL:5	c.1240-16236T>C		intron	N/A	ENSP00000490516.1	A0A1B0GVH5

Frequencies

GnomAD3 genomes AF: 0.905 AC: 136395 AN: 150654 Hom.: 61822 Cov.: 26

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.905 AC: 136492 AN: 150772 Hom.: 61860 Cov.: 26 AF XY: 0.906 AC XY: 66658 AN XY: 73536

African (AFR) AF: 0.850 AC: 34702 AN: 40810

American (AMR) AF: 0.934 AC: 14152 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3389 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5087 AN: 5098

South Asian (SAS) AF: 0.933 AC: 4426 AN: 4742

European-Finnish (FIN) AF: 0.903 AC: 9342 AN: 10342

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62299 AN: 67860

Other (OTH) AF: 0.926 AC: 1939 AN: 2094

Alfa AF: 0.915 Hom.: 27735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.11
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs4783824; hg19: chr16-53951661;