16-54063247-C-T

Variant names:

• chr16-54063247-C-T
• rs2689247
• NM_001080432.3:c.1365-48515C>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.1365-48515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,246 control chromosomes in the GnomAD database, including 521 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 0.069 (521 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

LOC105371271 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 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.1365-48515C>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1428-48515C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-48515C>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.1365-48515C>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.98-48515C>T		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.231-48515C>T		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10489 AN: 152128 Hom.: 519 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0690 AC: 10498 AN: 152246 Hom.: 521 Cov.: 32 AF XY: 0.0710 AC XY: 5287 AN XY: 74442

African (AFR) AF: 0.127 AC: 5257 AN: 41526

American (AMR) AF: 0.0476 AC: 728 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3472

East Asian (EAS) AF: 0.143 AC: 739 AN: 5174

South Asian (SAS) AF: 0.0872 AC: 421 AN: 4830

European-Finnish (FIN) AF: 0.0551 AC: 585 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2516 AN: 68026

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0292 Hom.: 24

Bravo AF: 0.0697

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.65
PhyloP100		1.5
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: rs2689247; hg19: chr16-54097159;