16-54024380-C-T

Variant names:

• chr16-54024380-C-T
• rs6499673
• NM_001080432.3:c.1365-87382C>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.1365-87382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,816 control chromosomes in the GnomAD database, including 7,796 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 0.31 (7796 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 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.1365-87382C>T		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1428-87382C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-87382C>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.1365-87382C>T		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000268349.7	TSL:1	c.97+39426C>T		intron	N/A	ENSP00000268349.7	X6R3I0
	FTO	ENST00000463855.1	TSL:1	c.231-87382C>T		intron	N/A	ENSP00000417843.1	Q9C0B1-2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47003 AN: 151696 Hom.: 7788 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.310 AC: 47064 AN: 151816 Hom.: 7796 Cov.: 32 AF XY: 0.314 AC XY: 23322 AN XY: 74172

African (AFR) AF: 0.371 AC: 15363 AN: 41388

American (AMR) AF: 0.387 AC: 5909 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3466

East Asian (EAS) AF: 0.376 AC: 1935 AN: 5148

South Asian (SAS) AF: 0.438 AC: 2101 AN: 4798

European-Finnish (FIN) AF: 0.266 AC: 2799 AN: 10518

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16980 AN: 67934

Other (OTH) AF: 0.297 AC: 625 AN: 2106

Alfa AF: 0.161 Hom.: 313

Bravo AF: 0.321

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-1.2
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: rs6499673; hg19: chr16-54058292;