rs2689243

chr16-54137344-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637969.1(FTO):c.1493-12343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,042 control chromosomes in the GnomAD database, including 20,506 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 0.49 (20506 hom., cov: 33)
• Consequence: FTO ENST00000637969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000612285.2	c.518-14770C>T		intron_variant		5
FTO	ENST00000637969.1	c.1493-12343C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73857 AN: 151922 Hom.: 20459 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.486 AC: 73955 AN: 152042 Hom.: 20506 Cov.: 33 AF XY: 0.487 AC XY: 36162 AN XY: 74306

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.454

Alfa AF: 0.382 Hom.: 11512

Bravo AF: 0.500

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.067
Dann	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2689243; hg19: chr16-54171256;