16-53985774-G-A

Variant names:

• chr16-53985774-G-A
• rs12324955
• NM_001080432.3:c.1364+51665G>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+51665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,074 control chromosomes in the GnomAD database, including 8,567 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 (8567 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 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+51665G>A		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1427+51665G>A		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+51665G>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+51665G>A		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.97+820G>A		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.230+51665G>A		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47592 AN: 151958 Hom.: 8526 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.314 AC: 47694 AN: 152074 Hom.: 8567 Cov.: 33 AF XY: 0.312 AC XY: 23163 AN XY: 74346

African (AFR) AF: 0.493 AC: 20444 AN: 41458

American (AMR) AF: 0.298 AC: 4562 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.155 AC: 800 AN: 5176

South Asian (SAS) AF: 0.226 AC: 1093 AN: 4826

European-Finnish (FIN) AF: 0.278 AC: 2934 AN: 10566

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16227 AN: 67972

Other (OTH) AF: 0.285 AC: 600 AN: 2108

Alfa AF: 0.263 Hom.: 15667

Bravo AF: 0.325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.40
PhyloP100		-2.2
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: rs12324955; hg19: chr16-54019686;