16-53781249-T-G

Variant names:

• chr16-53781249-T-G
• rs11075987
• NM_001080432.3:c.46-28891T>G

Variant summary

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

The NM_001080432.3(FTO):​c.46-28891T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,146 control chromosomes in the GnomAD database, including 26,882 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 0.58 (26882 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 23 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.46-28891T>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.46-28891T>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-28891T>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-28891T>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.46-28891T>G		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.46-28891T>G		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88334 AN: 152028 Hom.: 26837 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.581 AC: 88426 AN: 152146 Hom.: 26882 Cov.: 33 AF XY: 0.577 AC XY: 42920 AN XY: 74386

African (AFR) AF: 0.773 AC: 32086 AN: 41514

American (AMR) AF: 0.473 AC: 7235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2094 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3347 AN: 5174

South Asian (SAS) AF: 0.483 AC: 2324 AN: 4816

European-Finnish (FIN) AF: 0.486 AC: 5145 AN: 10588

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34437 AN: 67982

Other (OTH) AF: 0.565 AC: 1194 AN: 2112

Alfa AF: 0.528 Hom.: 68550

Bravo AF: 0.588

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		0.58
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: rs11075987; hg19: chr16-53815161;