chr16-53793267-C-G

Variant names:

• chr16-53793267-C-G
• rs9931494
• NM_001080432.3:c.46-16873C>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.46-16873C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,992 control chromosomes in the GnomAD database, including 9,547 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 (9547 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 36 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.46-16873C>G		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.46-16873C>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-16873C>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-16873C>G		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000637969.1	TSL:5	c.46-16873C>G		intron	N/A	ENSP00000490516.1	A0A1B0GVH5
	FTO	ENST00000918264.1		c.46-16873C>G		intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51083 AN: 151874 Hom.: 9546 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.336 AC: 51099 AN: 151992 Hom.: 9547 Cov.: 32 AF XY: 0.335 AC XY: 24918 AN XY: 74286

African (AFR) AF: 0.175 AC: 7270 AN: 41470

American (AMR) AF: 0.307 AC: 4694 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1868 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5166

South Asian (SAS) AF: 0.390 AC: 1876 AN: 4814

European-Finnish (FIN) AF: 0.406 AC: 4275 AN: 10520

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28837 AN: 67950

Other (OTH) AF: 0.350 AC: 739 AN: 2114

Alfa AF: 0.388 Hom.: 1398

Bravo AF: 0.317

Asia WGS AF: 0.314 AC: 1088 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.56
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9931494; hg19: chr16-53827179;