chr16-54137344-C-T

Variant names:

• chr16-54137344-C-T
• rs2689243
• ENST00000637969.1:c.1493-12343C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000637969.1	c.1493-12343C>T		intron_variant	Intron 9 of 10	5		ENSP00000490516.1
FTO	ENST00000612285.2	c.518-14770C>T		intron_variant	Intron 4 of 4	5		ENSP00000490300.1

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;