chr16-53787501-T-C

Variant names:

• chr16-53787501-T-C
• rs7206629
• NM_001080432.3:c.46-22639T>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.46-22639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,342 control chromosomes in the GnomAD database, including 14,996 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 0.44 (14996 hom., cov: 29)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• Publications: 20 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.46-22639T>C		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.46-22639T>C		intron_variant	Intron 1 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66333 AN: 151224 Hom.: 14977 Cov.: 29

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.439 AC: 66394 AN: 151342 Hom.: 14996 Cov.: 29 AF XY: 0.434 AC XY: 32062 AN XY: 73888

African (AFR) AF: 0.529 AC: 21775 AN: 41150

American (AMR) AF: 0.347 AC: 5279 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1883 AN: 3462

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5146

South Asian (SAS) AF: 0.395 AC: 1892 AN: 4788

European-Finnish (FIN) AF: 0.406 AC: 4249 AN: 10456

Middle Eastern (MID) AF: 0.376 AC: 109 AN: 290

European-Non Finnish (NFE) AF: 0.426 AC: 28873 AN: 67842

Other (OTH) AF: 0.425 AC: 895 AN: 2106

Alfa AF: 0.425 Hom.: 22548

Bravo AF: 0.433

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.86
PhyloP100		-0.98
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: rs7206629; hg19: chr16-53821413;