rs28562191

Variant names:

• chr16-53765391-C-T
• rs28562191
• NM_001080432.3:c.46-44749C>T

Variant summary

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

The NM_001080432.3(FTO):​c.46-44749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,154 control chromosomes in the GnomAD database, including 13,421 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 (13421 hom., cov: 28)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 12 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

LOC124903691 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-44749C>T		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.46-44749C>T		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63049 AN: 151032 Hom.: 13411 Cov.: 28

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.417 AC: 63092 AN: 151154 Hom.: 13421 Cov.: 28 AF XY: 0.415 AC XY: 30640 AN XY: 73820

African (AFR) AF: 0.423 AC: 17414 AN: 41162

American (AMR) AF: 0.349 AC: 5308 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1001 AN: 5078

South Asian (SAS) AF: 0.411 AC: 1953 AN: 4748

European-Finnish (FIN) AF: 0.431 AC: 4504 AN: 10442

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29571 AN: 67756

Other (OTH) AF: 0.419 AC: 881 AN: 2102

Alfa AF: 0.392 Hom.: 1555

Asia WGS AF: 0.331 AC: 1147 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.61
PhyloP100		0.61
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: rs28562191; hg19: chr16-53799303;