rs2689243

Variant names:

• chr16-54137344-C-T
• rs2689243
• ENST00000637969.1:c.1493-12343C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637969.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000637969.1	TSL:5	c.1493-12343C>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000612285.2	TSL:5	c.518-14770C>T		intron	N/A	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

African (AFR) AF: 0.776 AC: 32204 AN: 41492

American (AMR) AF: 0.399 AC: 6090 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2681 AN: 5168

South Asian (SAS) AF: 0.366 AC: 1768 AN: 4826

European-Finnish (FIN) AF: 0.402 AC: 4242 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24469 AN: 67950

Other (OTH) AF: 0.454 AC: 957 AN: 2106

Alfa AF: 0.399 Hom.: 16758

Bravo AF: 0.500

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.067
DANN	Benign	0.50
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs2689243; hg19: chr16-54171256;