rs11076022

Variant names:

• chr16-54117066-A-G
• rs11076022
• NM_001080432.3:c.*5151A>G

Variant summary

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

The NM_001080432.3(FTO):​c.*5151A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,096 control chromosomes in the GnomAD database, including 10,141 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 0.34 (10140 hom., cov: 32)
  • Exomes 𝑓: 0.31 (1 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*5151A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.*5151A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001080432.3	ENSP00000418823.1
FTO	ENST00000637969.1	c.1492+5177A>G		intron_variant	Intron 9 of 10	5		ENSP00000490516.1
FTO	ENST00000612285.2	c.517+5177A>G		intron_variant	Intron 4 of 4	5		ENSP00000490300.1
FTO	ENST00000637845.1	n.1493-1315A>G		intron_variant	Intron 9 of 10	5		ENSP00000489638.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52235 AN: 151962 Hom.: 10139 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

African (AFR) AF: 0.250 AC: 1 AN: 4

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) AF: 0.400 AC: 4 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.344 AC: 52258 AN: 152080 Hom.: 10140 Cov.: 32 AF XY: 0.350 AC XY: 26019 AN XY: 74346

African (AFR) AF: 0.158 AC: 6542 AN: 41518

American (AMR) AF: 0.386 AC: 5896 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2666 AN: 5162

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4818

European-Finnish (FIN) AF: 0.487 AC: 5153 AN: 10574

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28133 AN: 67950

Other (OTH) AF: 0.345 AC: 729 AN: 2112

Alfa AF: 0.338 Hom.: 6125

Bravo AF: 0.332

Asia WGS AF: 0.357 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.79
PhyloP100		-1.1
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: rs11076022; hg19: chr16-54150978;