rs1077129

Variant names:

• chr16-53757499-G-A
• rs1077129
• NM_001080432.3:c.46-52641G>A

Variant summary

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

The NM_001080432.3(FTO):​c.46-52641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,098 control chromosomes in the GnomAD database, including 12,183 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 0.39 (12183 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 2 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

LOC124903691 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-52641G>A		intron_variant	Intron 1 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.46-52641G>A		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58903 AN: 151020 Hom.: 12191 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.390 AC: 58890 AN: 151098 Hom.: 12183 Cov.: 32 AF XY: 0.389 AC XY: 28680 AN XY: 73776

African (AFR) AF: 0.264 AC: 10862 AN: 41206

American (AMR) AF: 0.391 AC: 5910 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3470

East Asian (EAS) AF: 0.189 AC: 972 AN: 5134

South Asian (SAS) AF: 0.342 AC: 1643 AN: 4806

European-Finnish (FIN) AF: 0.444 AC: 4563 AN: 10282

Middle Eastern (MID) AF: 0.468 AC: 132 AN: 282

European-Non Finnish (NFE) AF: 0.465 AC: 31556 AN: 67800

Other (OTH) AF: 0.428 AC: 896 AN: 2094

Alfa AF: 0.417 Hom.: 1474

Bravo AF: 0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.25
PhyloP100		-0.22
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: rs1077129; hg19: chr16-53791411;