16-53842654-C-T

Variant names:

• chr16-53842654-C-T
• rs7205213
• NM_001080432.3:c.752-1501C>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.752-1501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,674 control chromosomes in the GnomAD database, including 17,054 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 (17054 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 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.752-1501C>T		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.752-1501C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.782-1501C>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.752-1501C>T		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000637969.1	TSL:5	c.752-1501C>T		intron	N/A	ENSP00000490516.1	A0A1B0GVH5
	FTO	ENST00000918264.1		c.752-1501C>T		intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70775 AN: 151556 Hom.: 17035 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.467 AC: 70845 AN: 151674 Hom.: 17054 Cov.: 32 AF XY: 0.466 AC XY: 34546 AN XY: 74138

African (AFR) AF: 0.536 AC: 22147 AN: 41300

American (AMR) AF: 0.557 AC: 8496 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1592 AN: 3464

East Asian (EAS) AF: 0.518 AC: 2669 AN: 5150

South Asian (SAS) AF: 0.556 AC: 2680 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2678 AN: 10522

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28847 AN: 67868

Other (OTH) AF: 0.503 AC: 1059 AN: 2104

Alfa AF: 0.448 Hom.: 2667

Bravo AF: 0.493

Asia WGS AF: 0.556 AC: 1934 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.28
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: rs7205213; hg19: chr16-53876566;