rs2192872

Variant names:

• chr16-54040715-T-C
• rs2192872
• NM_001080432.3:c.1365-71047T>C

Variant summary

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

The NM_001080432.3(FTO):​c.1365-71047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,048 control chromosomes in the GnomAD database, including 20,556 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 0.48 (20550 hom., cov: 32)
  • Exomes 𝑓: 0.57 (6 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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]

ENSG00000261049 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-71047T>C		intron_variant	Intron 8 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-71047T>C		intron_variant	Intron 8 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73540 AN: 151900 Hom.: 20493 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.567 AC: 17 AN: 30 Hom.: 6 Cov.: 0 AF XY: 0.550 AC XY: 11 AN XY: 20

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.485 AC: 73656 AN: 152018 Hom.: 20550 Cov.: 32 AF XY: 0.491 AC XY: 36467 AN XY: 74300

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.420

Alfa AF: 0.429 Hom.: 2672

Bravo AF: 0.497

Asia WGS AF: 0.506 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2192872; hg19: chr16-54074627;