16-54070588-G-A

Position:

• chr16-54070588-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.1365-41174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,916 control chromosomes in the GnomAD database, including 5,788 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 0.27 (5788 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39

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]

LOC105371271 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-41174G>A		intron_variant		ENST00000471389.6	NP_001073901.1
LOC105371271	XR_933590.3	n.15442-1711G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-41174G>A		intron_variant		1	NM_001080432.3	ENSP00000418823	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40921 AN: 151798 Hom.: 5784 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.237

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.269 AC: 40939 AN: 151916 Hom.: 5788 Cov.: 32 AF XY: 0.275 AC XY: 20439 AN XY: 74206

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.235

Alfa AF: 0.253 Hom.: 1572

Bravo AF: 0.266

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.65

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: rs16952987; hg19: chr16-54104500;