16-53715057-T-G

Variant names:

• chr16-53715057-T-G
• rs12447481
• NM_001080432.3:c.45+10828T>G

Variant summary

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

The NM_001080432.3(FTO):​c.45+10828T>G variant causes a intron change. The variant allele was found at a frequency of 0.0595 in 152,266 control chromosomes in the GnomAD database, including 477 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 0.060 (477 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 9 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=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.45+10828T>G		intron_variant	Intron 1 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.45+10828T>G		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9054 AN: 152148 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0595 AC: 9063 AN: 152266 Hom.: 477 Cov.: 32 AF XY: 0.0609 AC XY: 4532 AN XY: 74466

African (AFR) AF: 0.0197 AC: 820 AN: 41564

American (AMR) AF: 0.0547 AC: 837 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1592 AN: 5168

South Asian (SAS) AF: 0.0860 AC: 415 AN: 4826

European-Finnish (FIN) AF: 0.0711 AC: 755 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0622 AC: 4232 AN: 68012

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0619 Hom.: 159

Bravo AF: 0.0587

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.81
PhyloP100		3.8
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: rs12447481; hg19: chr16-53748969;