16-53985009-G-A

Variant names:

• chr16-53985009-G-A
• rs16952730
• NM_001080432.3:c.1364+50900G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080432.3(FTO):​c.1364+50900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 455,684 control chromosomes in the GnomAD database, including 25,315 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 (7829 hom., cov: 31)
  • Exomes 𝑓: 0.33 (17486 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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.1364+50900G>A		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1427+50900G>A		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+50900G>A		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.1364+50900G>A		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.97+55G>A		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.230+50900G>A		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46843 AN: 151746 Hom.: 7820 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.325 AC: 98750 AN: 303818 Hom.: 17486 AF XY: 0.322 AC XY: 55741 AN XY: 172994

African (AFR) AF: 0.274 AC: 2351 AN: 8580

American (AMR) AF: 0.461 AC: 12531 AN: 27166

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 3598 AN: 10764

East Asian (EAS) AF: 0.719 AC: 6616 AN: 9206

South Asian (SAS) AF: 0.316 AC: 18838 AN: 59586

European-Finnish (FIN) AF: 0.281 AC: 3593 AN: 12768

Middle Eastern (MID) AF: 0.333 AC: 924 AN: 2776

European-Non Finnish (NFE) AF: 0.287 AC: 45602 AN: 158752

Other (OTH) AF: 0.330 AC: 4697 AN: 14220

GnomAD4 genome AF: 0.309 AC: 46870 AN: 151866 Hom.: 7829 Cov.: 31 AF XY: 0.313 AC XY: 23227 AN XY: 74192

African (AFR) AF: 0.262 AC: 10842 AN: 41396

American (AMR) AF: 0.397 AC: 6059 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3688 AN: 5138

South Asian (SAS) AF: 0.328 AC: 1578 AN: 4806

European-Finnish (FIN) AF: 0.289 AC: 3052 AN: 10552

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19477 AN: 67938

Other (OTH) AF: 0.335 AC: 702 AN: 2098

Alfa AF: 0.300 Hom.: 8880

Bravo AF: 0.319

Asia WGS AF: 0.481 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.72
PhyloP100		1.7
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: rs16952730; hg19: chr16-54018921;