chr16-54068854-G-A

Position:

• chr16-54068854-G-A

Variant summary

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

The NM_001080432.3(FTO):​c.1365-42908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,720 control chromosomes in the GnomAD database, including 7,052 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 0.25 (7052 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTO	NM_001080432.3	c.1365-42908G>A		intron_variant		ENST00000471389.6
LOC105371271	XR_933590.3	n.15442-3445G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTO	ENST00000471389.6	c.1365-42908G>A		intron_variant		1	NM_001080432.3	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37412 AN: 151602 Hom.: 7013 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.247 AC: 37517 AN: 151720 Hom.: 7052 Cov.: 31 AF XY: 0.247 AC XY: 18287 AN XY: 74124

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.236

Alfa AF: 0.168 Hom.: 954

Bravo AF: 0.259

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1420318; hg19: chr16-54102766;