16-53991260-G-A

Variant names:

• chr16-53991260-G-A
• rs8056199
• NM_001080432.3:c.1364+57151G>A

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+57151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,968 control chromosomes in the GnomAD database, including 16,683 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 0.46 (16682 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• 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

ENSG00000280392 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.485 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+57151G>A		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1427+57151G>A		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+57151G>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+57151G>A		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.97+6306G>A		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.230+57151G>A		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70496 AN: 151834 Hom.: 16660 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.250 AC: 4 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.286 AC XY: 4 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.464 AC: 70565 AN: 151952 Hom.: 16682 Cov.: 32 AF XY: 0.466 AC XY: 34575 AN XY: 74268

African (AFR) AF: 0.460 AC: 19045 AN: 41400

American (AMR) AF: 0.494 AC: 7548 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3464

East Asian (EAS) AF: 0.293 AC: 1511 AN: 5162

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4824

European-Finnish (FIN) AF: 0.591 AC: 6233 AN: 10554

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31462 AN: 67960

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.448 Hom.: 31013

Bravo AF: 0.459

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.20
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: rs8056199; hg19: chr16-54025172;