chr16-54085980-T-C

Variant names:

• chr16-54085980-T-C
• rs1008400
• NM_001080432.3:c.1365-25782T>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.1365-25782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,942 control chromosomes in the GnomAD database, including 21,409 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 0.53 (21409 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 14 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 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.1365-25782T>C		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1428-25782T>C		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-25782T>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.1365-25782T>C		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.98-25782T>C		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.231-25782T>C		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80228 AN: 151824 Hom.: 21406 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.528 AC: 80277 AN: 151942 Hom.: 21409 Cov.: 32 AF XY: 0.528 AC XY: 39216 AN XY: 74242

African (AFR) AF: 0.481 AC: 19930 AN: 41410

American (AMR) AF: 0.489 AC: 7471 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2978 AN: 5142

South Asian (SAS) AF: 0.563 AC: 2715 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5780 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37967 AN: 67968

Other (OTH) AF: 0.553 AC: 1166 AN: 2110

Alfa AF: 0.549 Hom.: 90607

Bravo AF: 0.518

Asia WGS AF: 0.534 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.7
DANN	Benign	0.37
PhyloP100		0.16
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: rs1008400; hg19: chr16-54119892;