rs1588413

Positions:

• chr16-54115620-G-A

Variant summary

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

The NM_001080432.3(FTO):​c.*3705G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,962 control chromosomes in the GnomAD database, including 1,999 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 0.15 (1998 hom., cov: 31)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*3705G>A		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.*3705G>A		3_prime_UTR_variant	9/9	1	NM_001080432.3	ENSP00000418823.1
FTO	ENST00000637969.1	c.1492+3731G>A		intron_variant		5		ENSP00000490516.1
FTO	ENST00000612285.2	c.517+3731G>A		intron_variant		5		ENSP00000490300.1
FTO	ENST00000637845.1	n.1493-2761G>A		intron_variant		5		ENSP00000489638.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22505 AN: 151602 Hom.: 1991 Cov.: 31

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.108 AC: 26 AN: 240 Hom.: 1 Cov.: 0 AF XY: 0.112 AC XY: 19 AN XY: 170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.148 AC: 22520 AN: 151722 Hom.: 1998 Cov.: 31 AF XY: 0.151 AC XY: 11185 AN XY: 74124

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.175

Alfa AF: 0.166 Hom.: 2002

Bravo AF: 0.147

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.80

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: rs1588413; hg19: chr16-54149532;