16-54119187-A-T

Variant names:

• chr16-54119187-A-T
• rs2075205
• NM_001080432.3:c.*7272A>T

Variant summary

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

The NM_001080432.3(FTO):​c.*7272A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,094 control chromosomes in the GnomAD database, including 9,456 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 0.32 (9456 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 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.*7272A>T		3_prime_UTR	Exon 9 of 9	NP_001073901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.*7272A>T		3_prime_UTR	Exon 9 of 9	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.1492+7298A>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000612285.2	TSL:5	c.517+7298A>T		intron	N/A	ENSP00000490300.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48512 AN: 151970 Hom.: 9460 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.319 AC: 48502 AN: 152090 Hom.: 9456 Cov.: 32 AF XY: 0.325 AC XY: 24157 AN XY: 74306

African (AFR) AF: 0.0871 AC: 3619 AN: 41530

American (AMR) AF: 0.367 AC: 5613 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2499 AN: 5154

South Asian (SAS) AF: 0.287 AC: 1378 AN: 4808

European-Finnish (FIN) AF: 0.484 AC: 5107 AN: 10550

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27867 AN: 67976

Other (OTH) AF: 0.326 AC: 688 AN: 2110

Alfa AF: 0.348 Hom.: 1248

Bravo AF: 0.303

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		0.19
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: rs2075205; hg19: chr16-54153099;