rs7188250

chr16-53800695-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):c.46-9445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,822 control chromosomes in the GnomAD database, including 8,653 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 0.31 (8653 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.46-9445T>C		intron_variant		ENST00000471389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.46-9445T>C		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46803 AN: 151702 Hom.: 8654 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.308 AC: 46793 AN: 151822 Hom.: 8653 Cov.: 33 AF XY: 0.306 AC XY: 22705 AN XY: 74126

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.333

Alfa AF: 0.365 Hom.: 1501

Bravo AF: 0.290

Asia WGS AF: 0.279 AC: 969 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.6
Dann	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs7188250; hg19: chr16-53834607;