rs9940128

Positions:

• chr16-53766842-G-A
• chr16-53766842-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.46-43298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,796 control chromosomes in the GnomAD database, including 13,350 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 0.42 (13350 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

LOC124903691 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.46-43298G>A		intron_variant		ENST00000471389.6
LOC124903691	XR_007065070.1	n.219+1667C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.46-43298G>A		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63099 AN: 151678 Hom.: 13340 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 63142 AN: 151796 Hom.: 13350 Cov.: 31 AF XY: 0.414 AC XY: 30688 AN XY: 74170

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.418

Alfa AF: 0.426 Hom.: 17258

Bravo AF: 0.403

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs9940128; hg19: chr16-53800754;