16-54055160-T-C

Variant names:

• chr16-54055160-T-C
• rs8062891
• NM_001080432.3:c.1365-56602T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.1365-56602T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,174 control chromosomes in the GnomAD database, including 49,820 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 0.80 (49820 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 7 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

LOC105371271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1365-56602T>C		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1428-56602T>C		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-56602T>C		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1365-56602T>C		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.98-56602T>C		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.231-56602T>C		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121704 AN: 152056 Hom.: 49753 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.801 AC: 121832 AN: 152174 Hom.: 49820 Cov.: 32 AF XY: 0.804 AC XY: 59832 AN XY: 74396

African (AFR) AF: 0.951 AC: 39514 AN: 41548

American (AMR) AF: 0.824 AC: 12594 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5163 AN: 5180

South Asian (SAS) AF: 0.850 AC: 4099 AN: 4822

European-Finnish (FIN) AF: 0.719 AC: 7605 AN: 10574

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.707 AC: 48032 AN: 67972

Other (OTH) AF: 0.782 AC: 1652 AN: 2112

Alfa AF: 0.722 Hom.: 39641

Bravo AF: 0.815

Asia WGS AF: 0.927 AC: 3223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
DANN	Benign	0.48
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8062891; hg19: chr16-54089072;