rs12597712

Variant names:

• chr16-54118708-G-C
• rs12597712
• NM_001080432.3:c.*6793G>C

Variant summary

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

The NM_001080432.3(FTO):​c.*6793G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,902 control chromosomes in the GnomAD database, including 11,681 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 0.38 (11678 hom., cov: 31)
  • Exomes 𝑓: 0.42 (3 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*6793G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.*6793G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58220 AN: 151748 Hom.: 11671 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.421 AC: 16 AN: 38 Hom.: 3 Cov.: 0 AF XY: 0.375 AC XY: 9 AN XY: 24

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.384 AC: 58268 AN: 151864 Hom.: 11678 Cov.: 31 AF XY: 0.391 AC XY: 28989 AN XY: 74180

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.381

Alfa AF: 0.399 Hom.: 1534

Bravo AF: 0.373

Asia WGS AF: 0.424 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.72

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: rs12597712; hg19: chr16-54152620;