rs3751812

Variant names:

• chr16-53784548-G-T
• rs3751812
• NM_001080432.3:c.46-25592G>T

Variant summary

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

The NM_001363894.2(FTO):​c.46-25592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,008 control chromosomes in the GnomAD database, including 8,219 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 0.30 (8219 hom., cov: 31)
• Consequence: FTO NM_001363894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• Publications: 233 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363894.2. 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.46-25592G>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.46-25592G>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-25592G>T		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.46-25592G>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.46-25592G>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000918264.1		c.46-25592G>T		intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45326 AN: 151890 Hom.: 8221 Cov.: 31

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.298 AC: 45312 AN: 152008 Hom.: 8219 Cov.: 31 AF XY: 0.298 AC XY: 22128 AN XY: 74278

African (AFR) AF: 0.0993 AC: 4121 AN: 41494

American (AMR) AF: 0.274 AC: 4180 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.152 AC: 782 AN: 5156

South Asian (SAS) AF: 0.312 AC: 1501 AN: 4812

European-Finnish (FIN) AF: 0.399 AC: 4201 AN: 10540

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27584 AN: 67948

Other (OTH) AF: 0.322 AC: 677 AN: 2102

Alfa AF: 0.375 Hom.: 34673

Bravo AF: 0.276

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.68
PhyloP100		0.59
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: rs3751812; hg19: chr16-53818460;