chr16-54067549-G-T

Position:

• chr16-54067549-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080432.3(FTO):​c.1365-44213G>T variant causes a intron change. The variant allele was found at a frequency of 0.198 in 152,204 control chromosomes in the GnomAD database, including 3,717 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 0.20 (3717 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42

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]

LOC105371271 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1365-44213G>T		intron_variant		ENST00000471389.6
LOC105371271	XR_933590.3	n.15441+3607G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1365-44213G>T		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30126 AN: 152086 Hom.: 3721 Cov.: 33

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.198 AC: 30114 AN: 152204 Hom.: 3717 Cov.: 33 AF XY: 0.197 AC XY: 14631 AN XY: 74416

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.240

Alfa AF: 0.234 Hom.: 1629

Bravo AF: 0.201

Asia WGS AF: 0.312 AC: 1086 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.85

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: rs12600060; hg19: chr16-54101461;