16-53779455-T-G

Variant names:

• chr16-53779455-T-G
• rs17817449
• NM_001080432.3:c.46-30685T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080432.3(FTO):​c.46-30685T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,026 control chromosomes in the GnomAD database, including 11,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11497 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176
• Publications: 380 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 16-53779455-T-G is Benign according to our data. Variant chr16-53779455-T-G is described in ClinVar as Benign. ClinVar VariationId is 225824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.46-30685T>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.46-30685T>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-30685T>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-30685T>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.46-30685T>G		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.46-30685T>G		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58339 AN: 151908 Hom.: 11489 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.384 AC: 58367 AN: 152026 Hom.: 11497 Cov.: 32 AF XY: 0.381 AC XY: 28308 AN XY: 74304

African (AFR) AF: 0.394 AC: 16348 AN: 41454

American (AMR) AF: 0.306 AC: 4682 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3466

East Asian (EAS) AF: 0.152 AC: 785 AN: 5170

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4824

European-Finnish (FIN) AF: 0.399 AC: 4215 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27722 AN: 67946

Other (OTH) AF: 0.385 AC: 812 AN: 2108

Alfa AF: 0.389 Hom.: 49735

Bravo AF: 0.373

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.9
DANN	Benign	0.65
PhyloP100		-0.18
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: rs17817449; hg19: chr16-53813367;