chr16-53785965-C-T

Variant names:

• chr16-53785965-C-T
• rs11075989
• NM_001080432.3:c.46-24175C>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.46-24175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 148,714 control chromosomes in the GnomAD database, including 12,747 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 0.41 (12747 hom., cov: 28)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 39 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-24175C>T		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.46-24175C>T		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 60713 AN: 148630 Hom.: 12735 Cov.: 28

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.408 AC: 60745 AN: 148714 Hom.: 12747 Cov.: 28 AF XY: 0.404 AC XY: 29150 AN XY: 72226

African (AFR) AF: 0.479 AC: 19435 AN: 40534

American (AMR) AF: 0.315 AC: 4700 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1749 AN: 3450

East Asian (EAS) AF: 0.151 AC: 765 AN: 5076

South Asian (SAS) AF: 0.318 AC: 1493 AN: 4696

European-Finnish (FIN) AF: 0.394 AC: 3708 AN: 9422

Middle Eastern (MID) AF: 0.378 AC: 108 AN: 286

European-Non Finnish (NFE) AF: 0.409 AC: 27538 AN: 67362

Other (OTH) AF: 0.403 AC: 831 AN: 2062

Alfa AF: 0.399 Hom.: 4539

Bravo AF: 0.401

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.2
DANN	Benign	0.36
PhyloP100		-0.63
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: rs11075989; hg19: chr16-53819877;