16-53912292-A-T

Variant names:

• chr16-53912292-A-T
• rs12708942
• NM_001080432.3:c.1240-21693A>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.1240-21693A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,266 control chromosomes in the GnomAD database, including 58,632 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 0.88 (58632 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.1240-21693A>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1302+11590A>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1270-21693A>T		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.1240-21693A>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000463855.1	TSL:1	c.105+808A>T		intron	N/A	ENSP00000417843.1
	FTO	ENST00000637969.1	TSL:5	c.1240-21693A>T		intron	N/A	ENSP00000490516.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133160 AN: 152148 Hom.: 58601 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.875 AC: 133247 AN: 152266 Hom.: 58632 Cov.: 32 AF XY: 0.877 AC XY: 65258 AN XY: 74444

African (AFR) AF: 0.764 AC: 31729 AN: 41526

American (AMR) AF: 0.917 AC: 14037 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3354 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5158 AN: 5172

South Asian (SAS) AF: 0.912 AC: 4401 AN: 4828

European-Finnish (FIN) AF: 0.901 AC: 9567 AN: 10618

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61935 AN: 68028

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.889 Hom.: 7491

Bravo AF: 0.871

Asia WGS AF: 0.948 AC: 3298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.52
PhyloP100		0.081
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: rs12708942; hg19: chr16-53946204;