chr16-54060218-C-T

Position:

• chr16-54060218-C-T

Variant summary

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

The NM_001080432.3(FTO):​c.1365-51544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,088 control chromosomes in the GnomAD database, including 4,406 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 0.19 (4406 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1365-51544C>T		intron_variant		ENST00000471389.6	NP_001073901.1
LOC105371271	XR_933590.3	n.11717C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1365-51544C>T		intron_variant		1	NM_001080432.3	ENSP00000418823	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28476 AN: 151970 Hom.: 4371 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.188 AC: 28569 AN: 152088 Hom.: 4406 Cov.: 33 AF XY: 0.186 AC XY: 13827 AN XY: 74344

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.179

Alfa AF: 0.112 Hom.: 1347

Bravo AF: 0.200

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.74

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: rs8049933; hg19: chr16-54094130;