chr16-54104652-A-G

Variant names:

• chr16-54104652-A-G
• rs2689269
• NM_001080432.3:c.1365-7110A>G

Variant summary

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

The ENST00000471389.6(FTO):​c.1365-7110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,906 control chromosomes in the GnomAD database, including 17,131 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 0.47 (17131 hom., cov: 31)
• Consequence: FTO ENST00000471389.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471389.6. 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.1365-7110A>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1428-7110A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-7110A>G		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.1365-7110A>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.98-7110A>G		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.231-7110A>G		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71374 AN: 151790 Hom.: 17101 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.470 AC: 71447 AN: 151906 Hom.: 17131 Cov.: 31 AF XY: 0.466 AC XY: 34594 AN XY: 74236

African (AFR) AF: 0.518 AC: 21438 AN: 41414

American (AMR) AF: 0.459 AC: 7000 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5154

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4372 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32425 AN: 67938

Other (OTH) AF: 0.462 AC: 971 AN: 2102

Alfa AF: 0.471 Hom.: 7833

Bravo AF: 0.474

Asia WGS AF: 0.305 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.50
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: rs2689269; hg19: chr16-54138564;