rs1421085

Positions:

• chr16-53767042-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080432.3(FTO):​c.46-43098T>C variant causes a intron change. The variant allele was found at a frequency of 0.308 in 152,026 control chromosomes in the GnomAD database, including 8,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.31 (8801 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 4.50

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-43098T>C		intron_variant		ENST00000471389.6	NP_001073901.1
LOC124903691	XR_007065070.1	n.219+1467A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.46-43098T>C		intron_variant		1	NM_001080432.3	ENSP00000418823	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46878 AN: 151908 Hom.: 8806 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.308 AC: 46862 AN: 152026 Hom.: 8801 Cov.: 32 AF XY: 0.309 AC XY: 22982 AN XY: 74308

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.338

Alfa AF: 0.391 Hom.: 24151

Bravo AF: 0.285

Asia WGS AF: 0.271 AC: 943 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

OBESITY (BMIQ14), SUSCEPTIBILITY TO Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.87

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: rs1421085; hg19: chr16-53800954;