16-54118136-A-T

Position:

• chr16-54118136-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.*6221A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,928 control chromosomes in the GnomAD database, including 19,041 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 0.49 (19041 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*6221A>T		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.*6221A>T		3_prime_UTR_variant	9/9	1	NM_001080432.3	ENSP00000418823	P1
FTO	ENST00000612285.2	c.517+6247A>T		intron_variant		5		ENSP00000490300
FTO	ENST00000637969.1	c.1492+6247A>T		intron_variant		5		ENSP00000490516
FTO	ENST00000637845.1	c.1493-245A>T		intron_variant, NMD_transcript_variant		5		ENSP00000489638

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74403 AN: 151808 Hom.: 19001 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.490 AC: 74499 AN: 151926 Hom.: 19041 Cov.: 31 AF XY: 0.494 AC XY: 36708 AN XY: 74264

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.457

Alfa AF: 0.465 Hom.: 1861

Bravo AF: 0.494

Asia WGS AF: 0.454 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.67

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: rs11076023; hg19: chr16-54152048;