16-53894167-G-C

Variant names:

• chr16-53894167-G-C
• rs12149433
• NM_001080432.3:c.1239+5216G>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.1239+5216G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,164 control chromosomes in the GnomAD database, including 58,703 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 0.88 (58703 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• Publications: 3 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.1239+5216G>C		intron_variant	Intron 7 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.1239+5216G>C		intron_variant	Intron 7 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133229 AN: 152046 Hom.: 58657 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.876 AC: 133329 AN: 152164 Hom.: 58703 Cov.: 32 AF XY: 0.876 AC XY: 65194 AN XY: 74392

African (AFR) AF: 0.785 AC: 32567 AN: 41480

American (AMR) AF: 0.921 AC: 14069 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3323 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4550 AN: 5182

South Asian (SAS) AF: 0.838 AC: 4034 AN: 4814

European-Finnish (FIN) AF: 0.903 AC: 9575 AN: 10608

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62139 AN: 68008

Other (OTH) AF: 0.908 AC: 1918 AN: 2112

Alfa AF: 0.897 Hom.: 7149

Bravo AF: 0.874

Asia WGS AF: 0.878 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.61
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: rs12149433; hg19: chr16-53928079;