rs12149010

Variant names:

• chr16-54074011-C-T
• rs12149010
• NM_001080432.3:c.1365-37751C>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.1365-37751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,908 control chromosomes in the GnomAD database, including 3,174 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 0.18 (3174 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 8 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

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 (NFE) allele frequency at 95% confidence interval = 0.256 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1365-37751C>T		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1428-37751C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-37751C>T		intron	N/A	NP_001350820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1365-37751C>T		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000268349.7	TSL:1	c.98-37751C>T		intron	N/A	ENSP00000268349.7	X6R3I0
	FTO	ENST00000463855.1	TSL:1	c.231-37751C>T		intron	N/A	ENSP00000417843.1	Q9C0B1-2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26977 AN: 151788 Hom.: 3177 Cov.: 31

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.178 AC: 26972 AN: 151908 Hom.: 3174 Cov.: 31 AF XY: 0.175 AC XY: 13023 AN XY: 74256

African (AFR) AF: 0.0429 AC: 1780 AN: 41444

American (AMR) AF: 0.160 AC: 2436 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5170

South Asian (SAS) AF: 0.159 AC: 766 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2612 AN: 10522

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17616 AN: 67908

Other (OTH) AF: 0.184 AC: 389 AN: 2114

Alfa AF: 0.231 Hom.: 2353

Bravo AF: 0.163

Asia WGS AF: 0.0750 AC: 260 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		-0.17
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: rs12149010; hg19: chr16-54107923;