16-53833547-C-T

Variant names:

• chr16-53833547-C-T
• rs2388405
• NM_001080432.3:c.751+7056C>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.751+7056C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,834 control chromosomes in the GnomAD database, including 16,437 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 0.46 (16437 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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.751+7056C>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.751+7056C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.781+7026C>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.751+7056C>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.751+7056C>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.751+7056C>T		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69508 AN: 151714 Hom.: 16415 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.458 AC: 69578 AN: 151834 Hom.: 16437 Cov.: 33 AF XY: 0.455 AC XY: 33790 AN XY: 74194

African (AFR) AF: 0.537 AC: 22206 AN: 41390

American (AMR) AF: 0.471 AC: 7191 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1590 AN: 3464

East Asian (EAS) AF: 0.578 AC: 2972 AN: 5146

South Asian (SAS) AF: 0.553 AC: 2663 AN: 4816

European-Finnish (FIN) AF: 0.236 AC: 2485 AN: 10540

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28762 AN: 67892

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.474 Hom.: 4755

Bravo AF: 0.476

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-0.61
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: rs2388405; hg19: chr16-53867459; COSMIC: COSV67114546;