16-53858061-T-C

Variant names:

• chr16-53858061-T-C
• rs8063241
• NM_001080432.3:c.895+13763T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.895+13763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,912 control chromosomes in the GnomAD database, including 15,357 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 0.40 (15357 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.895+13763T>C		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.895+13763T>C		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.925+13763T>C		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.895+13763T>C		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.895+13763T>C		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.895+13763T>C		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61094 AN: 151796 Hom.: 15297 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.403 AC: 61217 AN: 151912 Hom.: 15357 Cov.: 32 AF XY: 0.403 AC XY: 29899 AN XY: 74238

African (AFR) AF: 0.658 AC: 27246 AN: 41420

American (AMR) AF: 0.475 AC: 7244 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3466

East Asian (EAS) AF: 0.756 AC: 3907 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2423 AN: 10502

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17151 AN: 67960

Other (OTH) AF: 0.370 AC: 781 AN: 2112

Alfa AF: 0.295 Hom.: 7162

Bravo AF: 0.437

Asia WGS AF: 0.535 AC: 1837 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.67
PhyloP100		-0.63
Mutation Taster		=93/7	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: rs8063241; hg19: chr16-53891973;