rs2540766

Positions:

• chr16-54072059-G-A
• chr16-54072059-G-T

Variant summary

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

The NM_001080432.3(FTO):​c.1365-39703G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,132 control chromosomes in the GnomAD database, including 1,246 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 0.099 (1246 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-39703G>A		intron_variant		ENST00000471389.6	NP_001073901.1
LOC105371271	XR_933590.3	n.15442-240G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-39703G>A		intron_variant		1	NM_001080432.3	ENSP00000418823	P1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15060 AN: 152006 Hom.: 1238 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0804

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0992 AC: 15097 AN: 152124 Hom.: 1246 Cov.: 32 AF XY: 0.100 AC XY: 7435 AN XY: 74376

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0585

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0494 Hom.: 137

Bravo AF: 0.103

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.75

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: rs2540766; hg19: chr16-54105971;