rs708255

Variant names:

• chr16-54088601-G-A
• rs708255
• NM_001080432.3:c.1365-23161G>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.1365-23161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,030 control chromosomes in the GnomAD database, including 23,827 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 0.55 (23827 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 5 publications found

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]

FTO Gene-Disease associations (from GenCC):

• lethal polymalformative syndrome, Boissel type

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-23161G>A		intron_variant	Intron 8 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-23161G>A		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82934 AN: 151912 Hom.: 23792 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.546 AC: 83024 AN: 152030 Hom.: 23827 Cov.: 33 AF XY: 0.543 AC XY: 40359 AN XY: 74292

African (AFR) AF: 0.735 AC: 30497 AN: 41490

American (AMR) AF: 0.440 AC: 6719 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1616 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2074 AN: 5178

South Asian (SAS) AF: 0.485 AC: 2337 AN: 4822

European-Finnish (FIN) AF: 0.481 AC: 5077 AN: 10560

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32992 AN: 67938

Other (OTH) AF: 0.549 AC: 1158 AN: 2110

Alfa AF: 0.524 Hom.: 2816

Bravo AF: 0.547

Asia WGS AF: 0.458 AC: 1592 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.034
DANN	Benign	0.76
PhyloP100		-2.0
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

Other links and lift over

dbSNP: rs708255; hg19: chr16-54122513;