chr16-53969893-C-T

Variant names:

• chr16-53969893-C-T
• rs8053888
• NM_001080432.3:c.1364+35784C>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.1364+35784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,006 control chromosomes in the GnomAD database, including 20,299 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 0.51 (20299 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1364+35784C>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1427+35784C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+35784C>T		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1364+35784C>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.81-15045C>T		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.230+35784C>T		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77671 AN: 151888 Hom.: 20275 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.511 AC: 77736 AN: 152006 Hom.: 20299 Cov.: 32 AF XY: 0.509 AC XY: 37795 AN XY: 74276

African (AFR) AF: 0.540 AC: 22387 AN: 41446

American (AMR) AF: 0.595 AC: 9088 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3895 AN: 5150

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4814

European-Finnish (FIN) AF: 0.369 AC: 3894 AN: 10564

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32540 AN: 67962

Other (OTH) AF: 0.534 AC: 1129 AN: 2114

Alfa AF: 0.499 Hom.: 3124

Bravo AF: 0.533

Asia WGS AF: 0.577 AC: 2007 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.80
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8053888; hg19: chr16-54003805;