rs2072518

Positions:

• chr16-54118818-A-G
• chr16-54118818-A-T

Variant summary

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

The NM_001080432.3(FTO):​c.*6903A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,028 control chromosomes in the GnomAD database, including 10,779 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 0.36 (10775 hom., cov: 31)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*6903A>G		3_prime_UTR_variant	9/9	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.*6903A>G		3_prime_UTR_variant	9/9	1	NM_001080432.3	ENSP00000418823	P1
FTO	ENST00000612285.2	c.517+6929A>G		intron_variant		5		ENSP00000490300
FTO	ENST00000637969.1	c.1492+6929A>G		intron_variant		5		ENSP00000490516
FTO	ENST00000637845.1	c.*316+12A>G		intron_variant, NMD_transcript_variant		5		ENSP00000489638

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54573 AN: 151886 Hom.: 10770 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.500 AC: 12 AN: 24 Hom.: 4 Cov.: 0 AF XY: 0.556 AC XY: 10 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.550

GnomAD4 genome AF: 0.359 AC: 54601 AN: 152004 Hom.: 10775 Cov.: 31 AF XY: 0.366 AC XY: 27203 AN XY: 74244

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.360

Alfa AF: 0.394 Hom.: 6809

Bravo AF: 0.345

Asia WGS AF: 0.407 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.063
DANN	Benign	0.34

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: rs2072518; hg19: chr16-54152730;