rs17823223

Variant names:

• chr16-53965726-C-T
• rs17823223
• NM_001080432.3:c.1364+31617C>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.1364+31617C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,182 control chromosomes in the GnomAD database, including 907 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 0.093 (907 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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.1364+31617C>T		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1427+31617C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+31617C>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.1364+31617C>T		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000268349.7	TSL:1	c.81-19212C>T		intron	N/A	ENSP00000268349.7	X6R3I0
	FTO	ENST00000463855.1	TSL:1	c.230+31617C>T		intron	N/A	ENSP00000417843.1	Q9C0B1-2

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14143 AN: 152060 Hom.: 907 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0929 AC: 14134 AN: 152178 Hom.: 907 Cov.: 32 AF XY: 0.0879 AC XY: 6539 AN XY: 74418

African (AFR) AF: 0.0242 AC: 1005 AN: 41532

American (AMR) AF: 0.107 AC: 1630 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4820

European-Finnish (FIN) AF: 0.0559 AC: 592 AN: 10588

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9567 AN: 67990

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.110 Hom.: 826

Bravo AF: 0.0943

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		-0.38
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: rs17823223; hg19: chr16-53999638;