rs8050136

Variant names:

• chr16-53782363-C-A
• rs8050136
• NM_001080432.3:c.46-27777C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.46-27777C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,066 control chromosomes in the GnomAD database, including 12,270 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 0.40 (12270 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-27777C>A		intron_variant	Intron 1 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.46-27777C>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60202 AN: 151948 Hom.: 12261 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.396 AC: 60234 AN: 152066 Hom.: 12270 Cov.: 32 AF XY: 0.392 AC XY: 29148 AN XY: 74314

Gnomad4 AFR AF: 0.437 AC: 0.437422 AN: 0.437422

Gnomad4 AMR AF: 0.310 AC: 0.310325 AN: 0.310325

Gnomad4 ASJ AF: 0.505 AC: 0.504608 AN: 0.504608

Gnomad4 EAS AF: 0.152 AC: 0.151838 AN: 0.151838

Gnomad4 SAS AF: 0.314 AC: 0.314238 AN: 0.314238

Gnomad4 FIN AF: 0.399 AC: 0.399319 AN: 0.399319

Gnomad4 NFE AF: 0.408 AC: 0.407838 AN: 0.407838

Gnomad4 OTH AF: 0.391 AC: 0.390995 AN: 0.390995

Alfa AF: 0.395 Hom.: 58880

Bravo AF: 0.387

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs8050136; hg19: chr16-53816275;